Abstract: Methods of multi-protocol system and integrated circuit for multi-protocol communication on a single wire are provided. The method, adopted by a multi- protocol system containing a master device, a peripheral device and a slave device coupled together by a single wire, wherein the slave device is capable of operating in first and second operation modes. The method includes: receiving, by the slave device, an analog signal from the peripheral device on a single wire in the first operation mode; transmitting, by the master device, a digital signal containing a preamble pattern on the single wire; and after detecting the preamble pattern, switching, by the slave device, from the first to the second operation mode which includes suspending receiving the analog signal on the single wire, and communicating with the master device in serial digital data via the single wire.