"And they haven't invented a spell that our Hermione can't do."
Before she started her second year, Hermione wrote several letters to Harry, all of which were intercepted by Dobby, as the house-elf wanted Harry to believe that his friends had forgotten him in order to prevent his return to Hogwarts. She and her parents also accompanied Harry and the Weasley family to Diagon Alley to shop for school supplies.
It was during her second school year that Hermione first encountered the prejudice and hatred surrounding her blood status, when Draco Malfoy called her a "filthy little Mudblood" after she told him off for insulting the Gryffindor Quidditch team. Hermione had never heard the highly offensive term before, but others present had and lashed out at Draco. Fred and George Weasley lunged at him, and Ron even tried to hex him, but it backfired, as his wand had been damaged. To help Hermione feel better about the incident, Hagrid urged her not to think about it, pointing out that she was a talented witch, regardless of what bigoted people said about her Muggle-born status.
Hermione surprised Harry and Ron with her obvious crush on Gilderoy Lockhart, who became that year's Defence Against the Dark Arts Professor. She scored full marks on the first quiz in his class, which contained only questions pertaining to Lockhart's books, including a question regarding his favourite colour (lilac) that most of the class had answered incorrectly. In fact, she went as far as to doodle hearts on her D.A.D.A. assignments, not knowing until later that he was, in reality, a self-obsessed fraud.
On Halloween, 1992 Hermione attended Nearly Headless Nick's Death-day Party with Harry and Ron. While heading back upstairs, she followed Harry, who claimed to be hearing voices. They discovered the caretaker's cat petrified and the walls vandalised. Hermione began spending all her free time in the Hogwarts Library after she saw the vandalism on the corridor walls indicated that the Chamber of Secrets had been re-opened, hoping to read about the legend, but she could not as all the books were checked out. Hermione shocked everyone when she actually interrupted Professor Cuthbert Binns during a History of Magic lecture and asked him for information about it; this was the only known time when a student asked the boring professor a question, and the class was interested in what he had to say.
When Harry proposed the theory that Draco Malfoy was the "Heir of Slytherin," Hermione went even further by daring to check Moste Potente Potions out of the library using a note from Professor Lockhart, in the desire to research Polyjuice Potion. She hoped that they would be able to obtain a confession from Malfoy. She brewed the potion in Moaning Myrtle's bathroom, as no one used it. Hermione also risked serious consequences when she stole potion ingredients from Professor Snape's cupboards that were needed for the difficult potion.
Hermione: "Well, if you two are going to chicken out, fine. I don't want to break rules, you know. I think threatening Muggle-borns is far worse than brewing up a difficult potion. But if you don't want to find out..."
Ron: "I never thought I'd see the day when you'd be persuading us to break rules."
— Hermione convincing Harry and Ron of her plan to use Polyjuice Potion
Unfortunately, Hermione was unable to join Harry and Ron in the ruse with Polyjuice Potion because the hair she obtained from Millicent Bulstrode during their scuffle in the Duelling Club was actually the hair of Bulstrode's cat. Hermione grew fur and a tail, and remained in the hospital wing for weeks. Harry and Ron, however, were able to use the potion she brewed to transform into Gregory Goyle and Vincent Crabbe, respectively. They entered the Slytherin common room, and through conversation with Draco Malfoy, realized that he was not the Heir of Slytherin, and was not involved in the opening of the Chamber after all.
Months after her recovery from the Polyjuice complication, Hermione suffered another accident. Drawing the connection between Harry hearing voices in the walls and him being a Parselmouth, she came to the conclusion that the creature attacking students must be a Basilisk, and rushed to the library to conduct further research. On her way back from the library, she warned the first person she saw, Penelope Clearwater, and advised her to look around corners with a mirror before going anywhere. It saved both their lives, because they were both petrified when they spotted the basilisk's eyes through the mirror. Though she was petrified for the rest of the school year, Hermione was still able to assist Harry and Ron, for she had torn out the page on basilisks and scribbled on it pipes, referencing the manner in which the creature had moved around the school undetected. Using this note and other information they had gathered, Harry and Ron were able to successfully put an end to Lord Voldemort's plans to resurrect his body through his memory stored in an old school diary. Hermione was later cured with a Mandrake Restorative Draught created by Professor Sprout. She was disappointed to learn that, as a special treat for the school, Professor Dumbledore cancelled the students' end of year exams, though intensely proud that her friends had solved the mystery.
That summer, Hermione went on holiday to France with her parents. She was jealous of Ron when his family went to Egypt, as she felt it would be fascinating to study Ancient Egyptian wizardry.