Abstract: OBJECTIVE To investigate the correlation between human papillomavirus (HPV) 16 infection and colorectal cancer so as to provide theoretical basis for clinical prevention and treatment. METHODS A total of 148 patients with colorectal cancer who were treated in Nanyang Central Hospital from Sep 2013 to Sep 2015 were assigned as the colorectal cancer group, meanwhile, 140 healthy people who received the colonoscopy were chosen as the control group. The pathological tissues were collected from the two groups of participants, the positive rates of HPV16 were detected by using immunohistochemical method, and the statistical analysis of data was performed with the use of SPSS 19.0 software. RESULTS Of the 148 patients with colorectal cancer, 101 were detected positive for HPV16, with the positive rate 68.24%. Of the 140 healthy people in the control group, 15 were detected positive for HPV, with the positive rate 10.71%; the incidence rate of HPV infection of the colorectal cancer group was significantly higher than that of the control group (P<0.05). CONCLUSION The incidence of colorectal cancer is closely associated with the HPV16 infection, and the infection rate varies in the different clinical Dukes stages.