Objective To investigate the expression level of serum ubiquitin-conjugating enzyme 2C （UBE2C） and tripartite motif-containing protein 27 （TRIM27） in patients with endometrial cancer （EC） and their correlation with pathological parameters. Methods A total of 96 EC patients from March 2020 to March 2023 were selected as EC group； 65 patients with endometrial atypical hyperplasia （EAH） as EAH group， and 80 healthy subjects as the control group. Enzyme linked immunosorbent assay was applied to analyze the expression level of serum UBE2C and TRIM27. The relationship between serum UBE2C， TRIM27， and pathological data was analyzed； receiver operating characteristic was applied to evaluate the predictive value of serum UBE2C and TRIM27 level for EC. Results The level of serum UBE2C and TRIM27 of EC patients was obviously higher than that in healthy subjects （P < 0.05）， and was correlated with tumor diameter， tumor differentiation， lymph node metastasis， FIGO stage， muscle layer invasion depth， cervical involvement， estrogen receptor expression， and progestogen receptor expression （P < 0.05）. There was positive correlation between serum UBE2C and TRIM27 （r = 0.475， P < 0.001）； and the level of serum UBE2C and TRIM27 was positively correlated with tumor diameter， lymph node metastasis， FIGO stage， and depth of musclular invasion， but negatively with tumor differentiation， estrogen receptor expression， and progestogen receptor expression （P < 0.05）. The combination of UBE2C and TRIM27 had obviously higher AUC in evaluating EC than single detection （Z_{UBE2C-combination}=3.406， P < 0.001， Z_{TRIM27-combination} = 3.285， P = 0.001）. Conclusion The expression level of UBE2C and TRIM27 in serum of EC patients is up-regulated， which is closely related to pathological parameters. The level of serum UBE2C and TRIM27 can provide reference for early diagnosis of EC.