Human papillomavirus (HPV) infection is the second leading cause of cancer-associated morbidity and mortality among sexually active women worldwide due to its prerequisite role in cervical carcinogenesis. However, HPV infection alone is not sufficient to bring about cervical cancer. Sexual behaviour is consistently the most important co-factor for HPV infection and cervical cancer, but what is the underlying biological basis? In this paper, we postulate that human semen is the biological basis of sexual behaviour to promote HPV infection and cervical cancer. Based on international collaboration of epidemiological investigations and various HPV-infected in vivo models, it is likely for us to explore the exact role and pathogenesis of human semen in HPV infection and cervical carcinogenesis. If our hypothesis is true, regular use of condoms in the sexual intercourse should be recommended as a way of preventing genital transmission of HPV and reducing the incidence of cervical cancer, no matter women are infected by HPV or not.