High‐risk papillomavirus (HR‐HPV) testing combined with cytology improves the detection of cervical lesions and increases length of screening intervals. For a population‐based HR‐HPV survey, testing automation is in great need. The Cobas 4800 HPV Test System is a fully automated assay that can simultaneously detect HPV16, HPV18, and other 12 pooled HR‐HPV genotypes. This system has been employed for HR‐HPV screening in a number of countries; however, such application in a large population in China has not been documented. In this study, we employed the Cobas 4800 HPV Test System to detect HR‐HPV in cervical cytology specimens collected from a total of 5650 asymptomatic women from a region of South China. We reported the following: (1) the prevalence of the 14 genotypes of HR‐HPV was 12.96%; (2) for those with HR‐HPV infection, 2.25% were positive for HPV16, 0.50% for HPV18, 9.15% for pooled 12 HPV types, and 1.06% for multiple HPV infection; and (3) there was no significant difference in the HR‐HPV prevalence among different age groups. HPV16 and HPV18 have been shown to be the predominant HPV types found in cervical cancer patients in some regions in China, indicating that a fully automated assay like the Cobas 4800 HPV Test System is especially valuable for population‐based HR‐HPV screening in these regions as this assay can concurrently detect HPV16 and HPV18.