Objective To investigate whether berberine can enhance the chemotherapeutic sensitivity of temozolomide to glioma cells and its mechanism. Methods CCK-8 method was used to determine the effect of Ber and TMZ at different concentrations on glioma cell proliferation, and to evaluate the combined effect of Ber and TMZ. Flow cytometry was used to detect the effects of different concentrations of Ber, TMZ and the combination of the two on apoptosis and cell cycle of glioma cells. The expression of long non-coding RNA (LncRNA) CASC-2 in glioma cells was determined by RT-PCR. Results CCK 8 determination results show that the single use of Ber (5, 10, 20, 40, 80, 160 umol/L) and TMZ (25, 50, 100, 200, 400, 800 umol/L) separate effect on gliomas are a dose dependent inhibition of glioma proliferation, and concentration of Ber for 40 umol/L on glioma U87 cells as well as a significant inhibition will not lead to a large number of cell death, so after the experiment we use 40 umol/L study on combination of Ber. After 40umol/L Ber was combined with TMZ at different concentrations, cell survival rate decreased significantly compared with TMZ alone at the same concentration. The cell cycle detection by flow cytometry showed that after the action of Ber combined with TMZ on glioma, glioma cells could be largely blocked in S phase and inhibited to enter the proliferation phase. The results of flow cytometry showed that after TMZ combined with Ber, the apoptosis rate of glioma cells significantly increased compared with TMZ alone. The results of RT-PCR showed that the expression of CASC-2 in the combination group was higher than that in the single group, and it was significantly higher than that before the treatment. Conclusion Berberine can sensitize TMZ to the effect of chemotherapy on glioma. Berberine can increase the sensitivity of glioma to TMZ by up-regulating the expression of LncRNA CASC-2 gene。