Objective To study the effects of water extract of asparagus on the proliferation, apoptosis, migration, and invasion of human colorectal cancer cell line HCT116. Methods A CCK-8 assay, colony-forming experiment and EdU/ Hoechst 33258 fluorescent dye test were performed to detect the inhibitory effect of water extract of asparagus on the proliferation of human colorectal cancer HCT116 cells. The apoptosis rate was observed via Annexin V- FITC/ PI flow cytometry. The detection of cell migration and invasion were investigated by a wound healing test and Transwell invasion test, respectively. Real-time PCR was used to detect the mRNA levels of genes p53 and Bax. Results Compared with the control group cells, the HCT116 cells that had been treated with water extract of asparagus for 24 h were significantly fewer in number, adhered to the wall less firmly, and exhibited different degrees of nuclear pyknosis. The water extract of asparagus could inhibit the activity of HCT116 cells and promote apoptosis in a dose-dependent manner. The result of a colony formation test, EdU/ Hoechst 33258 fluorescence staining, wound healing test, and Transwell invasion test reveal that the water extract of asparagus inhibited cell proliferation, migration, and invasion. The Real-time PCR result show that the water extract of asparagus could upregulate the expression of apoptosis genes p53 and Bax. Conclusions The water extract of asparagus can inhibit the proliferation, migration, and invasion of colorectal cancer HCT116 cells, promote their apoptosis, and lead to the high expression of apoptosis genes p53 and Bax.