Abstract: Objective: To explore the effect of fish oil on the activity of cis-dichlorodiamineplatinum (Ⅱ) (CDDP) against A549 human lung adenocarcinoma cells and its protective effect on HEK293 cells damaged by CDDP. Methods: A549 and HEK293 cells were cultured in vitro, and the cells were divided into control group, CDDP group, fish oil group, fish oil+CDDP group; the cells were pretreated with different concentrations of fish oil, and CDDP injury models of CDDP group and fish oil+CDDP group were established at the same time. Cell viability was detected by CCK-8 method, and the kits were used to measure malondialdehyde (MDA) content, direduced glutathione (GSH) content, and superoxide dismutase (SOD) activity in HEK293 cells. Results: Fish oil at a concentration of 4~16 mg/L could significantly inhibit the cytotoxicity of HEK293 cells caused by CDDP (P<0.05). Fish oil at a concentration of 4 mg/L had the best protective effect, and fish oil at this concentration could significantly inhibit CDDP (20 mg/L) decreased GSH content and increased MDA content (P<0.05). When the fish oil concentration was ≥32 mg/L, the inhibitory effect of CDDP on A549 cells was significantly enhanced (P<0.05). Conclusion: Within a certain concentration range, fish oil has a certain protective effect on CDDP-induced damage to HEK293 of human embryonic kidney cells. Low-concentration fish oil has no obvious effect on the inhibitory effect of CDDP-induced A549 cells, and high-concentration fish oil enhances the anti-cancer effect of CDDP.