The present invention relates to a system and method for compensating for anode gain non-uniformity in a Multi-anode Position Sensitive Photomultiplier Tube (PS-PMT), in which a compensation unit is disposed between the multi-anode position sensitive photomultiplier tube and a position detection circuit unit and configured to uniform a current signal inputted to the position detection circuit unit, thereby compensating for anode gain non-uniformity. In accordance with the present invention, the compensation unit for changing resistance is used. Accordingly, there is an advantage in that the gain non-uniformity of each of the anodes of the PS-PMT can be compensated for. Furthermore, the gain non-uniformity of each of the anodes of the PS-PMT is compensated for by changing resistance values of the variable resistances of the compensation unit. Accordingly, there is an advantage in that the interaction positions of gamma rays can be calculated more precisely.