In conclusion, the present study demonstrated that ISL induced cell cycle arrest in the sub-G1 or G2/M phase of endometrial cancer cells via the p53/p21 signaling pathway and that ISL treatment suppressed HEC-1A-LUC xenograft tumor growth by inhibiting PCNA expression and increasing caspase-7, p62, and LC3B expression in tumor tissues. The gene discussed is SQSTM1; the disease is endometrial cancer.