Fluid flow in fractures is one of the important factors affecting rock mass stability. The fluid in the fracture not only produce external pressure but also weaken the fracture strength. Therefore, engineering accidents including slope instability and tunnel collapse frequently occur. In order to explore the mechanism of seepage on the block stability of fractured rock masses, this study proposes a stability analysis method considering both seepage force and effect of fracture strength weakening by water, based on the Key Block Theory (KBT). In this method, the fluid pressures in fractures are simulated by Unified Pipe-network Method (UPM), and the relationship between fracture strength,s weakening and fluid pressures is determined by an empirical formula. This method is adopted to study the influence of seepage on the stability of a fractured rock slope. Results show that the action modes of seepage pressure and fracture water weakening on slope stability of fractured rock masses are different. The seepage force affects both the anti-sliding force and sliding force of the block. Therefore, the influence of seepage force on the block stability is more complicated, including changes of the block stability states, sliding surface, and the instability pattern. Fracture water weakening only reduces the anti-sliding force of blocks, and then reduces the stability of block, while not change the instability pattern of unstable block. Moreover, there is generally a critical pressure which is the most dangerous for rock slope engineering.