ABSTRACT: Tobacco smoking is established as a cofactor of human papillomavirus (HPV) for cervical cancer risk. However, the role of secondhand smoking in cervical carcinogenesis is controversial. We aimed to assess the association between secondhand smoking and high risk- (HR-) HPV persistence, a pivotal event in development of cervical cancer. In total, 9,846 women who underwent health-screening examinations from 2002 to 2011 at the National Cancer Center, Korea, were included. Secondhand smoking was defined as being exposed to secondhand smoke at home or in the workplace. Multivariate logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for risks of HR-HPV infection at baseline (N, 9,846, negative vs. positive), 1-year persistence (n, 1,237, 1-year negative vs. 1-year persistence), and 2-year persistence (n, 481, 2-year negative vs. 2-year persistence). Active smoking, secondhand smoking, and secondhand smoking in nonactive smokers had no association with these risks. Among alcohol drinkers, secondhand smoking in nonactive smokers had higher risks of HR-HPV infection at baseline (OR = 1.25, 95% CI = 1.05-1.48, p for multiplicative interaction = 0.003), 1-year persistence (1.75, 1.14-2.68, 0.004), and 2-year persistence (2.96, 1.42-6.15, 0.006), when compared to HR-HPV negative, 1-year negative, and 2-year negative categories, respectively. However, among nonalcohol drinkers, there was no association between smoking or secondhand smoking status and these risks. These findings suggest that women exposed to secondhand smoking at home or in the workplace might be at high risk of HR-HPV persistence when it is combined with alcohol drinking, even though neither active smoking nor secondhand smoking independently affects the risk.