OBJECTIVES: To evaluate cost-effectiveness of different HPV vaccination as alternatives or additions to the current screening program to prevent and control cervical cancer in Mainland China. METHODS: A Markov model was developed for a cohort of 100,000 12-year-old girls to simulate the natural history of low risk and high risk to HPV infection and its progress to cervical cancer or genital warts. Three recommended screening (protocol 1. Liquid-based cytology test + HPV DNA test; protocol 2. Pap smear cytology test + HPV DNA test; protocol 3. Visual inspection with acetic acid) and two types of HPV vaccination programs (bivalent and quadrivalent vaccines) were incorporated to the two kinds of HPV vaccines. Input data were obtained from literature review, national databases, and a field study. Sensitivity analyses were performed on key variables and different vaccination scenarios. RESULTS: With 20% screen coverage and 20% vaccine coverage, quadrivalent vaccine plus screening by protocol 2 had the most attractive cost-effectiveness ratio ($6,691 per QALY saved) compared to when using a willingness to pay (WTP) for a QALY threshold of $22,433 (three times of GDP per capita in China). The bivalent vaccine and its combination with the screening program could reduce much more incidence and mortality of cervical cancer compared to the quadrivalent vaccine, while the cost per QALY acquired of the quadrivalent vaccine is lower