An over-current protection circuit includes a voltage generating unit and a comparing unit. The voltage generating unit is configured for receiving a first voltage and generating a reference voltage. The reference voltage has an offset positively dependent on temperature and negatively dependent on the first voltage, and the offset of the reference voltage varies along with another offset varying within a sense voltage sensed by the over-current protection circuit. The comparing unit is configured for comparing the reference voltage with the sense voltage to output a control signal for de-asserting the sense voltage when the sense voltage is correlated to an over-current condition of the sense voltage exceeding the reference voltage. A driver is also disclosed herein.