AIM: To investigate the molecular mechanism of a novel bromobenzene substituted trifluoromethylbenzo Cyclopentanone WW02 inhibiting the viability and proliferation of human lung cancer A549 and H1299 cells. METHODS: The effect of different concentrations of WW02 (6.25, 12.5, 25, 50 μg/mL) on cell viability and proliferation of A549 and H1299 were measured using CCK-8 and EdU methods. After 24 hours of stimulation of A549 and H1299 cells with different concentrations of WW02, the changes in Akt and mTOR phosphorylation levels under different concentrations of WW02 were detected through Western blot assay. Macromolecular docking was carried out between WW02, AKT and mTOR through MOE Dock. RESULTS: After treating A549 and H1299 cells with WW02 using different concentrations (6.25, 12.5, 25, 50 μg/mL), the activity of A549 and H1299 cells decreased in a concentration dependent manner compared with the DMSO control group (P<0.05). The proliferation of cells showed a concentration dependent decrease compared to the DMSO control group (P<0.05). Compared with the DMSO control group, after 24 hours of WW02 stimulation, the phosphorylation levels of Akt and mTOR in A549 cells decreased under the concentration of WW02 (12.5, 25, 50 μg/mL, P<0.05). Compared with the DMSO control group, the phosphorylation levels of Akt and mTOR in H1299 cells decreased after 24 hours of WW02 stimulation (25, 50 μg/mL, P<0.05). Based on pattern analysis, it was found that WW02 had a strong binding with Akt and mTOR, with the highest score of -8.3 kcal/mol for WW02 and mTOR, while the highest score for WW02 and Akt was -7.3 kcal/mol. CONCLUSION: WW02 inhibits the activity and proliferation of lung cancer A549 and H1299 cells, and its mechanism of action may be achieved by directly binding to Akt and mTOR proteins to inhibit Akt and mTOR phosphorylation.