Abstract: Objective To investigate the expression of related proteins in leiomyoma and leiomyosarcoma,and discuss the potential value in tumor genesis, treatment and prognosis monitoring in leiomyosarcoma. Methods Between 2006 and 2016, 14 leiomyosarcoma and 65 leiomyomas were collected, and all patients underwent operation and confirmed by pathology. ERα(Estrogen receptor α), ERβ, PR(progesterone receptor), PR-b, PTEN(Phosphatase and tensin homolog deleted from chromosome 10), m-TOR(mammalian target of rapamycin), HIF-1α(hypoxia induced factor 1α), GLUT-1(glucose transport proteins-1) and Ki-67(nuclear-associated antigen) were determined by immumo-histochemical staining in leiomyoma and uterine sarcoma tissue respectively. The difference between the groups about the expression of proteins were analyzed. Student's t test and Mann-Whitney test were performed in comparison between groups. The expression of m-TOR was tested by chi square. Results An increased immune-expression of HIF-1α(P=0.011), Ki-67(P<0.001), GLUT-1(P=0.028), m-TOR(P=0.019) and decreased expression of ERα(P<0.001), PR(P<0.001), PTEN(P=0.002) were observed in leiomyosarcoma as compared to leiomyoma. The expression of other proteins showed no significant difference. Chi square showed more leiomyosarcoma patients with higher expression of m-TOR(χ²=11.695,P=0.001)while other protein expressions exhibited no significant differences. Conclusion The different expression of ERα, GLUT-1 in leiomyoma and leiomyosarcoma provides a theoretical basis for noninvasive identification of leiomyosarcoma, and m-TOR, PTEN and other related proteins in the two tumors may provide potential therapeutic target and maybe an effective prognostic biomarker.