The American Cancer Society recommends the following:

Since the cause of many cases of anal cancer is unknown it is not possible to prevent this disease completely.

The best way to reduce the risk of developing anal cancer is to avoid infection with HPV or HIV. The risk of these infections is higher for those who have sex with multiple partners and those who have unprotected anal sex.

Infection with HPV increases the risk of developing anal cancer. Uncircumcised men are thought to be more likely to have the virus and be able to pass it on to someone else. Infection with HPV can be present for years without any symptoms; so the absence of visible warts cannot be used to tell if someone has HPV. Even when someone doesn't have warts (or any other symptom), he (or she) can still be infected with HPV and pass the virus to somebody else.

Condoms ("rubbers") do provide some protection against HPV, but they cannot completely protect against infection. This is because HPV can still be passed from one person to another by skin-to-skin contact with an HPV-infected area of the body that is not covered by a condom — like the skin in the genital or anal area. Still, it is important to use condoms to protect against AIDS and other sexually transmitted illnesses that are passed on through some body fluids.

A vaccine called Gardasil® can help protect against infection with HPV subtypes 16 and 18 (as well as 6 and 11). In studies, this vaccine was found to prevent genital warts caused by HPV types 6 and 11 and to prevent cervix cancers and precancers caused by types 16 and 18. This vaccine can only be used to prevent HPV infection — it does not help treat an existing infection. To be most effective, the vaccine should be given before a person becomes sexually active. It is currently only approved for use in women, but it is being looked at for possible use in males. While studies completed so far have concentrated on the vaccine's effectiveness against cervical pre-cancerous conditions, the hope is that this may eventually help prevent other cancers linked to HPV, including anal cancers.

Smoking is a known risk factor for anal cancer. Stopping smoking significantly reduces the risk of developing anal cancer and many other cancers.