Abstract: To study the protective effects of plant active substances on cell damage induced by PM_2.5, PM_2.5 samples were collected from downtown Beijing to study its effects on Chinese hamster ovary cells (CHO). Chlorogenic acid, ferulic acid and orientin were selected to explore their protective effect on CHO cells. First, the test dose of PM_2.5 and the optimum protection doses of three types of phyto-active substances were determined by Cell Counting Kit-8 (CCK-8). The damage and protective effects of plant active substances were determined with comet assay, micronucleus assay, flow cytometry and Western Blotting. The results showed that PM_2.5 at 15 μg/mL resulted in significant DNA damage of CHO cells, micronuclei formation increase and decreased cell proliferation index caused by cell cycle arrest. Chlorogenic acid, ferulic acid and orientin at 50,0 and 10 μmol/L respectively had different levels of protective effects on DNA damage caused by PM_2.5. Nevertheless, PM_2.5 induced p53 and caspase-3 expression increased in CHO cells. On the contrary, ferulic acid, chlorogenic acid and orientin reduced these expressions to some extent. This suggests that cell damage caused by PM_2.5 was reduced by the pretreatments of 50 μmol/L chlorogenic acid, 20 μmol/L ferulic acid and 10 μmol/L orientin. Ferulic acid was the optimum antagonist against damage caused by PM_2.5, followed by chlorogenic acid and orientin. The latter was relatively poor.