The TPS55288 uses I²C interface for flexible converter parameter programming. I²C is a bi-directional 2-wire serial interface. Only two bus lines are required: a serial data line (SDA) and a serial clock line (SCL). I²C devices can be considered as masters or slaves when performing data transfers. A master is the device that initiates a data transfer on the bus and generates the clock signals to permit that transfer. At that time, any device addressed is considered a slave.

The TPS55288 operates as a slave device with address 74h and 75h set by a different resistor at the MODE pin. Receiving control inputs from the master device like a microcontroller or a digital signal processor reads and writes the internal registers 00h through 07h. The I²C interface of the TPS55288 supports both standard mode (up to 100 kbit/s) and fast mode plus (up to 1000 kbit/s). Both SDA and SCL must be connected to the positive supply voltage through current sources or pullup resistors. When the bus is free, both lines are in high voltage.