Objective The ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is a protein coding gene which is associated with colorectal cancer and other diseases. Therefore, the present study was aimed at investigating the effect and mechanism of UHRF1 protein on invasion and metastasis in human renal carcinoma cells. Methods After UHRF1 was interfered with or overexpressed in renal carcinoma cell lines A498 and 769-P, the relative mRNA and protein level of UHRF1 was detected by RT-qPCR and immunofluorescence. The colony formation assay and MTT were performed to observe the proliferation and cell viability in each group. In addition, the invasion and metastasis of the cells in each group were detected by Transwell and wound healing assay. Finally, Western blot was utilized to measure protein expression of MMP-2 and MMP-9 and the level of protein in the Wnt/ β -catenin signaling pathway. Results The cell ability, proliferation, invasion, and metastasis in A498 and 769-P cells were inhibited after interfering with UHRF1. In addition, the expression of MMP-2, MMP-9, c-myc, and β -catenin was significantly decreased, while the expression of GSK-3 β was significantly increased. However, contrasting results were demonstrated when UHRF1 was overexpressed. Conclusions Interference with the expression of UHRF1 was able to inhibit the invasion and metastasis of human renal carcinoma cell lines A498 and 769-P, which may be related to mediating the Wnt/ β -catenin signaling pathway and regulating the expression of MMP-2 and MMP-9.