For further programmability, the TUSB320 device can be controlled using I²C. The TUSB320 device local I²C interface is available for reading/writing after T_{I2C_EN} when the device is powered up. The SCL and SDA terminals are used for I²C clock and I²C data respectively. If I²C is the preferred method of control, the ADDR pin must be set accordingly.

The following procedure should be followed to write to TUSB320 I²C registers:

1. The controller initiates a write operation by generating a start condition (S), followed by the TUSB320 7-bit address and a zero-value R/W bit to indicate a write cycle
2. The TUSB320 device acknowledges the address cycle
3. The controller presents the sub-address (I²C register within the TUSB320 device) to be written, consisting of one byte of data, MSB-first
4. The TUSB320 device acknowledges the sub-address cycle
5. The controller presents the first byte of data to be written to the I²C register
6. The TUSB320 device acknowledges the byte transfer
7. The controller may continue presenting additional bytes of data to be written, with each byte transfer completing with an acknowledge from the TUSB320 device
8. The controller terminates the write operation by generating a stop condition (P)

The following procedure should be followed to read the TUSB320 I²C registers:

1. The controller initiates a read operation by generating a start condition (S), followed by the TUSB320 7-bit address and a one-value R/W bit to indicate a read cycle
2. The TUSB320 device acknowledges the address cycle
3. The TUSB320 device transmits the contents of the memory registers MSB-first starting at register 00h or last read sub-address+1. If a write to the T I²C register occurred prior to the read, then the TUSB320 device starts at the sub-address specified in the write.
4. The TUSB320 device waits for either an acknowledge (ACK) or a not-acknowledge (NACK) from the controller after each byte transfer; the I²C controller acknowledges reception of each data byte transfer
5. If an ACK is received, the TUSB320 device transmits the next byte of data
6. The controller terminates the read operation by generating a stop condition (P)

The following procedure should be followed for setting a starting sub-address for I²C reads:

1. The controller initiates a write operation by generating a start condition (S), followed by the TUSB320 7-bit address and a zero-value R/W bit to indicate a read cycle
2. The TUSB320 device acknowledges the address cycle
3. The controller presents the sub-address (I²C register within the TUSB320 device) to be read, consisting of one byte of data, MSB-first
4. The TUSB320 device acknowledges the sub-address cycle
5. The controller terminates the read operation by generating a stop condition (P)