The interference mechanisms between the rotor passage vortex and tip leakage vortex were analyzed numerically to control the secondary flow losses in a highly loaded rotor with a low aspect ratio and large camber angle. The impact of end-wall fillets on these losses was also investigated. The results revealed that, at the leading edge up to 50% axial chord length, after the horseshoe vortex was evolved and formed into the hub passage vortex, it quickly moved to the upper part of the blade, limiting the development of the shroud passage vortex and reducing the vorticity of the tip leakage vortex. After 50% axial chord length, the high-speed shear effects between the leakage flow and the mainstream were intensified, rapidly strengthening the tip leakage vortex. The shroud passage vortex was pushed away from the suction surface by the combined action of the hub passage vortex and tip leakage vortex, which prevented it from sucking low-energy fluid onto the suction surface and restricted its growth. Due to the entrainment effect of the passage vortex system, low-energy fluid was accumulated at the blade tip, increasing the flow losses and deviation angles there. As a result, the main cause of losses was attributed to the secondary flow caused by the end-wall. The effect of end-wall fillet on the highly loaded rotor with a low aspect ratio and large camber angle was significantly different from the traditional turbines. When the fillet radius was smaller than the boundary layer thickness at the leading edge of the hub, the fillet could weaken the strength of the horseshoe vortex and the hub passage vortex, but it could increase their influential region. This intensified the entrainment effect of the vortex system, reduced the accumulation of low-energy fluid within the 30%—50% axial chord length range on the suction surface, and increased the radial pressure gradient. Therefore, as the radial migration of the hub passage vortex decreased, its entrainment of low-energy fluid on the suction surface was reduced, resulting in reduced vorticity. When the fillet radius was larger than the boundary layer thickness at the leading edge of the hub, the fillet could weaken the effect region of the horseshoe vortex and the hub passage vortex, increasing the accumulation of low-energy fluid on the suction surface close to the blade root and decreasing the radial pressure gradient. Then the radial migration position and vorticity of the hub passage vortex increased, and low-energy fluid was accumulated on the suction surface. Consequently, turbine efficiency decreased as the fillet radius increased.