Objective To investigate the effect of lentivirus-mediated shRNA silencing of angiopoietin-like protein 4 (ANGPTL4) on the proliferation and apoptosis of cervical cancer SiHa cells. Methods The ANGPTL4 lentiviral vectors were used to transfect SiHa cells. Real-time quantitative PCR (qRT-PCR) and Western blotting were respectively used to detect ANGPTL4 expression at mRNA and protein levels. The proliferation ability of SiHa cells after transfection was assessed by MTT assay and colony formation assay. The cell cycle was examined by flow cytometry. The annexin V-phycoerythrin/7-aminoactinomycin D (annexin V-PE/7-AAD) staining combined with flow cytometry was used to examine the effect of ANGPTL4 silence on the apoptosis of SiHa cells. Results After the ANGPTL4 lentiviral vectors were transfected into SiHa cells, qRT-PCR and Western blotting showed that the expression of ANGPTL4 mRNA and protein were significantly inhibited in LV3-ANGPTL4 group. The MTT assay showed that the proliferation ability of SiHa cells in LV3-ANGPTL4 group was also inhibited. Colony formation assay revealed that the colony number in LV3-ANGPTL4 group was reduced. The cells in G0/G1 phase and the apoptosis rate increased in LV3-ANGPTL4 group. Conclusion The lentivirus-mediated ANGPTL4 shRNA can inhibit the proliferation, induce the cell cycle arrest in G0/G1 phase, and promote the apoptosis in SiHa cells.