Multi-cluster fracturing technology was often used in horizontal well reservoir reconstruction to achieve production increase, which also affected casing equivalent stress distribution. This paper focuses on multi-cluster fracturing and establishes a fracturing model in line with the reality. The three-dimensional finite element model of multi-cluster fracture-formation-cement sheath-casing was proposed, the influence of cluster spacing and fracturing cluster number on casing equivalent stress was studied. On this basis, a single segment 8-cluster three-dimensional finite element model was developed. The influence of rock elastic modulus, casing inner wall pressure, geostress change and elastic modulus of cement sheath on casing equivalent stress was simulated from two aspects of uniform and non-uniform extrusion of wellbore. Actual data was used and analyzed for the fracturing section of a well in Weirong Block, southern Sichuan Basin, China. The results showed that the casing equivalent stress decreased with the increase of fracture dip angle. The casing equivalent stress increased with the increase of cluster spacing; however, it decreased with the increase of rock elastic modulus. The casing equivalent stress increased with the increase of casing wall pressure. Also, the cracks extrude the casing evenly did not affect the change on casing equivalent stress. It was also found that, when casing was uniformly squeezed by multiple fractures, the difference of ground stress had little effect on casing equivalent stress, while non-uniform extrusion had greater effect on casing equivalent stress. Further, when there was no wellhead pumping pressure, the casing equivalent stress increased with the increase of the elastic modulus of the cement sheath, and decreased on the contrary. The elastic modulus of rock was lower than that of cement sheath, and the casing equivalent stress increased with the increase of the elastic modulus of cement sheath, and decreased on the contrary. The research results had certain guiding significance for the prevention and control of casing damage in fracturing section.