A method of operating a memory cell includes the following steps. A first plurality of bias operations is performed to the memory cell using a first voltage, wherein the memory cell comprises a variable resistance pattern, and the first voltage of each cycle of the first plurality of bias operations has a same first polarity. The memory cell is determined whether reaches a fatigue threshold. After the determination determines that the memory cell reaches the fatigue threshold, a second plurality of bias operations is performed to the memory cell using a second voltage, wherein the second voltage of each cycle of the second plurality of bias operations has a same second polarity, and the second polarity is opposite to the first polarity.