The invention discloses a display screen Mura phenomenon compensation method and device; the method comprises the following steps: taking gray scale frames of a first gray scale value and a second gray scale value of a display screen; calculating a gamma index value of each pixel according to the luminous intensity data of each pixel in each gray scale frame; calculating Mura data of each pixel according to the gamma index value of each pixel in an index or power function mode; carrying out Mura phenomenon compensation according to the calculated Mura data. The method and device can obtain a good Mura phenomenon compensation effect, thus optimizing the display effect.