We report a prevalence rate of 23.6% human papillomavirus (HPV) infection with oncogenic subtypes and 2.4% cervical intraepithelial neoplasia (CIN) III and cervical cancer (CC) in rural middle-aged women in 2 counties with the highest CC mortality in Shanxi Province, China. We examined the association of risk factors to HPV infection and to CIN III and CC in 8,798 unscreened women aged 35–50 years. Multivariate odds ratios (OR) and 95% confidence intervals (CI) for each endpoint were obtained for risk factors after adjustment for covariates. The OR of oncogenic HPV were: 1.41 (95% CI = 1.25–1.60) and 1.42 (95% CI = 1.24–1.61) for the participant and her husband having multiple sexual partners, respectively; 1.67 (95% CI = 1.37–2.04), 1.15 (95% CI = 1.04–1.26), and 0.82 (95% CI = 0.72–0.94) for ever (vs. never) diagnosed with tuberculosis, cervical inflammation and vaginal trichomoniasis, respectively; while bathing in a public (v. private) facility had an OR of 1.23 (95% CI =1.11–1.35). Seasonal fluctuations in HPV infection, but not CC, appeared in Xiangyuan County, with OR of 1.23 (95% CI = 1.14–1.33) and 1.51 (95% CI = 1.35–1.67) in Spring and Winter compared to Summer, respectively. The OR of CIN III and CC in the HPV positives were: 2.03 (95% CI = 1.63–2.53) for ages ≥45 years (vs. <40); and 4.01 (95% CI = 1.46–11.0) for ≥3 (vs. no) home births. Public health interventions and control strategies for improving the reproductive health of women in these rural populations need to be developed to reduce risk of HPV and subsequent CC. © 2005 Wiley-Liss, Inc.