Objective To investigate the impact of YTH N6 methyladenosine RNA binding protein 3 (YTHDF3) on the proliferation, migration, and apoptosis of human colorectal cancer cell line HCT-116. Methods The cells were divided into a negative control group, interference groups 1, 2, and 3. Small interfering RNA targeting YTHDF3 was transfected into colorectal cancer cells HCT-116. The expression of YTHDF3 in each group was assessed using qRT-PCR and Western blot analysis. Cell proliferation was evaluated using CCK-8 assay and plate cloning assay, while cell migration was assessed using transwell assay and scratch assay. Flow cytometry was used to measure cell apoptosis. Results The silencing efficiency of HCT-116 cells was validated through qRT-PCR and Western blot analysis. Transfection of small interfering YTHDF3 effectively reduced the expression of YTHDF3 in HCT-116 cells compared to the negative control group. Silencing YTHDF3 can significantly inhibited cell proliferation and migration while promoting apoptosis in HCT-116 cells. Conclusion Silencing YTHDF3 can decelerates cell proliferation and migration while enhancing apoptosis in HCT-116 cells.