Tracking multiple moving targets in video is still a challenge because of mutual occlusion problem. This paper presents a Gaussian mixture probability hypothesis density-based visual tracking system with game theory-based mutual occlusion handling. First, a two-step occlusion reasoning algorithm is proposed to determine the occlusion region. Then, the spatial constraint-based appearance model with other interacting targets¶ interferences is modeled. Finally, an n-person, non-zero-sum, non-cooperative game is constructed to handle the mutual occlusion problem. The individual measurements within the occlusion region are regarded as the players in the constructed game competing for the maximum utilities by using the certain strategies. The Nash Equilibrium of the game is the optimal estimation of the locations of the players within the occlusion region. Experiments conducted on publicly available videos demonstrate the good performance of the proposed occlusion handling algorithm.