Objective To investigate whether curcumin can reverse the progesterone resistance of human endometrial carcinoma ISH cell lines by regulating the Notch1 signaling pathway. Methods The human endometrial carcinoma progesterone resistant cell line ISH/MPA was established by increasing the concentration and long-term persistence of medroxyprogesterone acetate (MPA). The cell resistance index was detected by MTS method，the growth curve of ISH/MPA cells was plotted and the cell population doubling time was calculated. ISH/MPA cells were treated with different concentrations of curcumin (0，7.5，15，30，60 μmol/L)，and the survival rate of cells was detected by MTT assay. ISH/MPA Cells were divided into ISH/MPA group，curcumin group，agonist group，agonist+curcumin group，curcumin group added 30 μmol/L curcumin，agonist group added 2 μmol/L NSC 22423，agonist+curcumin group added 30 μmol/L curcumin and 2 μmol/L NSC22423，Cells in the ISH/MPA group were not treated.After 48 h，flow cytometry instrument detected cells apoptosis rate，western blot detected Notch1，Jagged1 and Hes-1 protein expression. Results The drug resistance index of ISH/MPA cells increased with the increasing concentration of MPA，and when the concentration of MPA was 10 μmol/L，the population doubling time of ISH and ISH/MPA cells had no statistical difference，and the growth curves of the two cells were basically the same. Different concentrations of curcumin decreased the survival rate of ISH/MPA cells，and increased with the increase of curcumin concentration (P<0.05). Compared with ISH/MPA group，the apoptosis rate of cells in curcumin group was increased，and the protein expressions of Notch1，Jagged1 and Hes -1 were decreased，the apoptosis rate of cells in agonist group was decreased，and the protein expressions of Notch1，Jagged1 and Hes -1 were increased (P< 0.05). Compared with curcumin group，the apoptosis rate of agonist + curcumin group was decreased，and the protein expressions of Notch1，Jagged1 and Hes -1 were increased (P<0.05). Compared with agonist group，the apoptosis rate of agonist+curcumin group increased，and the protein expressions of Notch1，Jagged1 and Hes -1 decreased (P<0.05). Conclusion Curcumin enhances the sensitivity of ISH cells to MPA，possibly by inhibiting the Notch1/Jagged1/ Hes-1 signaling pathway.