Objective: To investigate the effect of apolipoprotein M (ApoM) on the proliferation, migration, and invasion of renal clear cell carcinoma cell lines (ACHN, 769-P, and 786-O). Methods: To establish ApoM overexpression (ApoM-OE) cell models, lentivirus carrying human ApoM gene and negative control (NC) lentivirus were used to infect renal clear cell carcinoma cell lines respectively. CCK-8 assay and colony formation assay were employed to evaluate the proliferation capacity of renal cancer cells. Wound healing assay was used to detect the migration capacity of tumor cells and transwell assay was applied to examine the invasion ability. Results: The proliferation capacity of ApoM-OE groups was significantly reduced at 72 h in ACHN and 769-P cells (P<0.01, P<0.05, respectively). The difference in 786-O cell arises at 48 h (P<0.001). The colony formation assay indicated that the capacity of colony formation was significantly reduced in 3 renal carcinoma cell lines (P<0.001, P<0.01, P<0.01, respectively). Wound healing assay showed that the migration of ApoM-OE groups in ACHN and 769-P was restrained at 12 h (P<0.05, P<0.001, respectively); the migration of 786-O ApoM-OE group was suppressed at 24 h (P<0.01). Transwell assay found that the invasion of renal carcinoma cells was inhibited due to ApoM overexpression (P<0.001, P<0.001, P<0.01, respectively). Conclusion: ApoM significantly inhibites the proliferation, migration, and invasion capacity of renal carcinoma cells.