Background: Renal cell carcinoma (RCC) is a common cancer, accounting for about 2-3% of all adult cancers. A novel diagnostic biomarker and therapeutic target is urgently needed. However, the function of miR-451 in RCC remains unknown. Here, we explored the role of miR-451 in RCC. Material/Methods: MiR-451 levels in RCC tissues and cells were tested by qRT-PCR. Cells were transfected miR-451 mimics or miR-451 ASO by Lipofectamine. The cellular proliferation was tested by MTT analysis. The apoptosis rate was revealed by FACS. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-451. The PSMB8 protein level was tested by Western blot. The interaction between miR-451 and PSMB8 was confirmed by dual luciferase assays. Results: MiR-451 level of RCC tissues was lower than in normal tissues, which was correlated to the patients' survival rate. Low levels of miR-451 in RCC cells promoted the growth of cells and inhibited cells apoptosis and vice versa. The targeted gene of miR-451 is PSMB8. Conclusions: MiR-451 acts as an anti-oncogene in RCC. Our data offer a new therapeutic target for further research.