Objective To research the clinical application of ultrasonography combined with the detection of hs-CRP and CA125 in the diagnosis of endometrial cancer. Method 107 cases of endometrial carcinoma in our hospital were selected as the research objects. According to the FIGO staging criteria, they were divided into the stage Ⅰ~Ⅱ (58 cases) and the stageⅢ~Ⅳ (49 cases). The levels of serum hs-CRP, CA125 and the positive rate in different stages were compared. The diagnostic ability of ultrasonography combined with hs-CRP and CA125 in endometrial carcinoma were evaluated by ROC curve. Result The levels of hs-CRP and CA125 in patients with stage Ⅰ~Ⅱ were significantly lower than those of stage Ⅲ~Ⅳ, the FIGO staging was positively correlated with the levels of hs-CRP and CA125, and the differences were statistically significant. The positive rate of hs-CRP, CA125 and hs-CRP combined with CA125 in patients with stage Ⅰ~Ⅱ were were significantly lower than that those in stage Ⅲ~Ⅳ, the differences were statistically significant. The sensitivity and specificity of ultrasound combined with hs-CRP and CA125 was significantly greater than that of ultrasound combined with hs-CRP and ultrasound combined with CA125. Conclusion Transvaginal ultrasound can detect suspicious endometrial cancer lesions. Combined detection of serum hs-CRP and CA125 can helpful for the early diagnosis of endometrial cancer, and can significantly improve the clinical detection rate of endometrial cancer, thereby reducing the misdiagnosis and misdiagnosis.