〔Abstract〕 Objective To explore the inhibitory effect of sophocarpine on lung cancer cellsin vitroas well as its possible mechanism. Methods A549 cells were treated with different concentrations of sophocarpine, the IC50of sophocarpine to A549 was detected by MTT. The sophocarpine group was treated with proper concentration and the untreated A549 cells were used as the control group. Cell proliferation was detected by clone formation and BrdU, cell apoptosis was detected by TUNEL and flow cytometry, the expression of proliferating cell nuclear antigen(PCNA), MYC, Bax, Bcl-2, lipocalin type prostaglandin-D-synthase(L-PTGDS)and PTGDR2 was detected by Western blot. Besides, the PGD2 group was treated with 5 ng/ml PGD2 activator, clone formation, TUNEL and Western blot were performed to detect the effect of PGD2 on proliferation and apoptosis of A549 cells. Results The IC50of sophocarpine to A549 was 5.196 mmol/L, clone formation and BrdU experiment showed that the proliferation of A549 cells in the 5 mmol/L sophocarpine treated group was lower than that in the control group while the apoptosis of A549 cells was higher than that in the control group. The expression of PCNA, MYC, Bax, Bcl-2 was lower than that in the control group, while the expression of Bax was higher than that in the control group, all of the differences were statistically significant(P<0.05). The protein expression of L-PTGDS and PTGDR2 in sophocarpine group was higher than that in control group(P<0.05). The proliferation of A549 cells treated with 5 ng/ml PGD2 activator was inhibited, and apoptosis significantly increased(P<0.05). Conclusion Sophocarpine can inhibit the proliferation and promote the apoptosis of lung cancer cells, as well as activating PGD2/PTGDR2 pathway, thus inhibiting the occurrence of lung cancer.