Due to machining precision, spraying coating, cavitation, and erosion, walls of pump flow passage components have different roughness, which will affect the flow state near the wall and even the main flow. In the present work, four types of roughness Ra = 0, 0.1, 1, and 10 μm are set to investigate the influence of wall roughness on the interaction of leakage flow and main flow in a mixed flow pump with tip clearance. Results show that the interaction area of leakage flow and main flow can be divided into three regions: (a) tip clearance zone, (b) shear flow zone, and (c) primary vortex zone. In the tip clearance zone, as roughness increases, the velocity magnitude and its derivative at the same wall distance gradually decrease, and the velocity angle at blade tip continuously increases in the inner circular boundary layer. As the roughness increases, the leakage flow gradually decreases, especially in the center chord region. In the shear flow zone, the velocity gradient rapidly decreases along the direction of pressure side to suction side, and finally, it becomes stable. As roughness increases, the velocity gradient intensity decreases, and the main reason is that the differences of velocity magnitude and velocity direction between the inner circular boundary layer and potential region decrease. In the primary vortex zone, the tip leakage vortex core indicated by the Liutex vortex method coincides with the low-pressure core location. As the roughness increases, the tip leakage vortex core becomes closer to the next blade. The pressure coefficient and vorticity of the tip leakage vortex core decrease with increasing of roughness, and the slopes remain constant on different cross sections with value of 5.9 × 103 and 2.4 × 103 m−1, respectively.