A multiplex electrophoretic display driver circuit comprises a memory unit, a display controller and a voltage driving unit. The memory unit has two registers respectively storing the current and former gray-level matrix signals. The gray-level matrix signal contains gray-level data corresponding to electrophoretic pixels. The display controller has an encoding circuit and a counting circuit. The encoding circuit generates a difference-value matrix signal containing difference values according to a difference between the current and former gray-level matrix signals and then generates a voltage-difference matrix signal containing voltage-difference signals corresponding to the electrophoretic pixels. The counting circuit receives the difference-value matrix signal and counts to generate refreshing values corresponding to the difference values. The encoding circuit adds the refreshing values to a next-cycled difference-value matrix signal to generate a new voltage-difference matrix signal. The voltage driving unit drives the electrophoretic pixels according to the voltage-difference matrix signal.