An infrared control system and an operation method thereof are provided. The infrared control system includes a sound sensor, an infrared transmitter and a processing unit. In an initialization period, the processing unit controls the infrared transmitter to transmit a first infrared control code of a first control code set to a target device, and monitors an environment sound via the sound sensor to determine whether the target device responds to the first infrared control code. If the processing unit determines that the target device responds to the first infrared control code according to environment sound, the processing unit records a relationship between the first control code set and the target device.