Objective To investigate the clinical efficacy of medroxyprogesterone acetate combined with tamoxifen in the treatment of endometrial cancer and its effect on serum levels of TSGF, PRL and HE4.Methods 105 patients with endometrial cancer admitted to the hospital from March 2016 to December 2018 were randomly divided into 2 groups. 50 cases in the control group were treated with medroxyprogesterone acetate tablets, 55 cases in the observation group were treated with medroxyprogesterone acetate tablets combined with tamoxifen citrate tablets. After 12 weeks of treatment, the recent treatment effect and adverse reactions of the two groups were observed, and the expression levels of TSGF, PRL and HE4 in the serum of the two groups before and after treatment were detected by enzyme-linked immunosorbent assay (ELISA).Results After 12 weeks of treatment, the effective rate of the control group was 42.00%, the clinical benefit rate was 68.00%; the effective rate of the observation group was 65.45%, the clinical benefit rate was 85.45%; the difference of the effective rate and the clinical benefit rate between the two groups was statistically significant (P The results showed that the expression of TSGF, PRL and HE4 in the serum of the patients in the observation group was significantly lower than that in the control group (P<0.05); the incidence of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05).Conclusions Medroxyprogesterone acetate combined with tamoxifen can improve the clinical therapeutic effect of endometrial cancer and reduce the expression level of serum TSGF, PRL and HE4. Its clinical effect may be related to the expression of serum TSGF, PRL and HE4.