Abstract: Objective To investigate the effects of miR-153-3p on cell proliferation and angiogenesis in renal cell carcinoma (RCC) and its underlying mechanism.Methods The expression of miR-153-3p in RCC adjacent and tumor tissues was analyzed based on the TCGA database. The expression of miR-153-3p in normal human renal epithelial cell line (293T) and RCC cell lines (TK10, A498, UO31, 786-O, and 769-P) was detected by qRT-PCR. The binding sites between miR-153-3p and DLL4 were predicted using the TargetScan database and verified by dual-luciferase reporter assay. 786-O cells were divided into the following groups: a blank group, an NC group, a miR-153-3p mimic group, a miR-153-3p inhibitor group, a si-DLL4 group, and a miR-153-3p inhibitor + si-DLL4 group. The mRNA expression of miR-153-3p and DLL4/Notch pathway-related genes was detected by qRT-PCR. Cell proliferation was assessed by MTT assay, and angiogenesis was evaluated by tube formation assays.Results miR-153-3p was down-regulated in RCC tissues and cell lines. Overexpression of miR-153-3p enhanced RCC cell proliferation and angiogenesis, while inhibiting miR-153-3p weakened these effects. miR-153-3p negatively regulates DLL4 expression, suppressing the downstream expression of Notch1, Hes1, and Jagged1. Knockdown of DLL4 reversed the effects of miR-153-3p inhibitor.Conclusions miR-153-3p may inhibit RCC cell proliferation and angiogenesis by targeting and negatively regulating the DLL4-mediated Notch signaling pathway.