Background: No study has reported radiosensitizing effect of triptolide in lung cancer cell lines. We explored the effect and underlying molecular mechanisms of combined triptolide and irradiation treatment in lung cancer cell lines. Materials and Methods: Colony formation assays were conducted to test the radiosensitizing effect of triptolide in A549 and H460 lung cancer cell lines. Survival fractions and sensitizing enhancement ratios were calculated. To determine the underlying mechanism of triptolide and irradiation combination, immunofluorescence cytometric analysis of apoptosis was conducted after treatment with triptolide and/or 4 Gy irradiation. To explore the molecular mechanisms of apoptosis induced by triptolide and irradiation combined treatment, western blot analysis was conducted after treatment with triptolide and/or irradiation (1, 2, 3, or 4 Gy). The antibodies used for Western blotting were PARP, JNK, p53, HSP70, and Akt. Results: Combined triptolide and irradiation treatment significantly decreased the surviving fractions than irradiation alone in both cell lines. Triptolide and irradiation combination treatment also resulted in significant increase in apoptosis rates than irradiation alone in both cell lines. The expression of PARP cleavage, JNK, and p53 were prominent in the groups treated with triptolide and irradiation combination. The expression of HSP70 and Akt were suppressed in groups treated with the triptolide and irradiation combination. Conclusion: This study showed that triptolide in combination with irradiation enhanced antitumor effects in lung cancer cell lines.