Context.— Reports for atypical squamous cells of undetermined significance (ASC-US) and histologic findings are rare in China. Objective.— To analyze the correlation findings of ASC-US cytology with high-risk human papillomavirus (hrHPV) test and histopathologic follow-ups. Design.— ASC-US cases with hrHPV test and histologic follow-ups between 2011 and 2015 were analyzed at a College of American Pathologists–certified laboratory. Results.— A total of 2 206 588 Papanicolaou (Pap) tests were performed, including 1 513 265 liquid-based cytology preparations (68.58%), and 693 323 conventional Pap tests (31.42%). The overall ASC-US reporting rate was 3.77% (83 199 of 2 206 588), with the highest in women aged 40 to 49 years. Of 18 574 women with ASC-US Pap and HPV testing, the hrHPV positivity rate was 34.98% (6498 of 18 574) with the highest in women younger than 30 years. A total of 6012 women with ASC-US Pap test findings had histologic follow-ups within 6 months; the overall cervical intraepithelial neoplasia 2 and above (CIN2+) detection rate was 7.87% (473 of 6012). One thousand nine hundred nine women with ASC-US Pap and HPV testing had histologic results. CIN2+ lesion was found in 13.98% (124 of 887) of women with ASC-US Pap/HPV-positive test results, significantly higher than 2.84% (29 of 1022) for women with ASC-US Pap/HPV-negative test results. Cervical squamous cell carcinoma was found in 3.95% (35 of 887) of women with ASC-US/HPV-positive test results. Conclusions.— This is one of the largest studies to investigate HPV and histologic follow-up findings in women with ASC-US in China. The ASC-US reporting rate, HPV positivity rate, and CIN2+ detection rate were all within the currently recognized benchmark ranges. These findings may contribute to establishing a baseline for better understanding of the status of cervical screening in China.