Abstract: The per- and polyfluoroalkyl substances (PFASs) have received extensive social attention due to their potential hazards. The authors in this research took a megacity in Central China as the study object and adopted liquid chromatography-mass spectrometry to study the content and distribution pattern of PFASs in the main rivers and lakes in this area, and carried out a health risk assessment. The research results show that PFASs were detected in multiple water bodies, among which perfluorobutanesulfonic acid (PFBS) was the main pollutant. The pollution of S04, S06, S07 and S08 sites in the study area is relatively serious, and PFASs pollution in the surface water of this area belongs to medium degree compared with the surface water in other areas of China. The risk entropy values were used to evaluate the health risk, and the risk entropy values of PFBS, PFOA and PFOS in several sampling points of the study area range from 0.1 to 1, indicating a medium risk. Therefore, the health risk assessment and supervision of PFASs still require attentions in order to protect the ecological environment and human health.