An eFuse one-time programmable (OTP) memory is provided. The eFuse OTP memory supports inter integrated circuit (I2C) communication, and an operation method thereof. The eFuse OTP memory includes: an eFuse intellectual property (IP) which data writes once and data reads multiple times for a plurality of addresses; and an I2C slave which communicates with an I2C master based on a serial clock line and a serial data line, and performs the data write and the data read to and from the eFuse IP.