ABSTRACT: Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$ 10,958 (95% CI: $169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50% of school girls will prevent 13,854 (95% CI: 8,355 to 20,776) DALYs/year, but the corresponding incremental cost-effectiveness ratio (ICER, US$ 83,043, 95% CI: $52,234 to $138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction.