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The determination of PM 2.5 -induced biological response is essential for understanding the adverse health risk associated with PM 2.5 exposure. In this study, we conducted cell-based bioassays to measure the toxic effects of PM 2.5 exposure, including cytotoxicity, oxidative stress, genotoxicity and inflammatory response. The concentration-response relationship was analyzed by benchmark dose (BMD) modeling and the BMDL 10 was used to estimate the biological potency of PM 2.5 exposure. PM 2.5 samples were collected from three typical megacities of China (Beijing, BJ; Wuhan, WH; Guangzhou, GZ) in typical seasons (winter and summer). The total PM, water-soluble fractions (WSF), and organic extracts (OE) were prepared and subjected to examination of toxic effects. The biological potencies for cytotoxicity, oxidative stress and genotoxicity were generally higher in winter samples, while the inflammatory potency of PM 2.5 was higher in summer samples. The relative health risk (RHR) was determined by integration of the biological potencies and the cumulative exposure level, and the ranks of RHR were BJ-W > WH-W > BJ-S > WH-S > GZ-W > GZ-S. Notably, we note that different PM 2.5 compositions were associated with distinct biological effects, and the health effects distribution of PM 2.5 varied in regions and seasons. These findings demonstrate that the approach of integrated cell-based bioassays could be used for the evaluation of health effects of PM 2.5 exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)