An optimal location of perforation clusters is critical to obtain a commercial production rate in unconventional tight reservoir reservoirs. At present, the perforation cluster position design method based on overlapping induced stress between fractures is only suitable for multi-stage single-cluster fracturing in horizontal well. Under real well conditions, multiple fractures extend at the same time during multi-stage and multi-cluster fracturing, which is easy to produce stress barrier effects and stress interference effects. These problems put forward higher requirements for selecting the best position of perforating cluster. In this paper, according to the characteristics of multiple fractures extending simultaneously in one stage in multi-stage multi-cluster fracturing, the influence range of induced stress in one stage considering stress barrier and disturbance effect was analyzed. The mathematical model for calculating the induced stress at different locations in one stage is established considering the variation of effective net pressure to the surrounding formation and the resulted resulting distribution of induced stress. Based on this model, a multi-stage and multi-cluster fracture optimization design method for horizontal wells is proposed, which can effectively avoid repeated fractured and non-fractured areas by optimizing the non-equidistant locations of the perforated clusters. Case studies show that this method can effectively avoid refracturing and non-refracturing zones, thus achieving better fracturing results with lower energy consumption.