Objective To observe the therapeutic effect of the combination of Xiaoaiping injection and chemotherapy on advanced esophageal cancer and coagulation function. Methods 100 patients with advanced esophageal carcer were randomly divided into control group and observation group, and each group had 50 cases. The control group was treated with TP chemotherapy, and the observation group, on the basis of the control group’s treatment, was treated with the Xiaoaiping injection, and treatment effects, Karnofsky, adverse drug reactions and INR changes before and after the treatment of the two groups were observed. Results After 2 periods of treatment, the local control rate of solid tumor, Karnofsky score, and stability in the observation group were significantly higher than those in the control group (p<0.05); and the plasma prothrombin time (PT), activated partial coagulation activity time (APTT) and thrombin time (TT) were significantly lower in the observation group than in the control group (p<0.05), and Fibrinogen (FIB) was significantly higher than the control group (p<0.05); and there was no statistically significant difference in the incidence of adverse reactions between the two groups (p>0.05). Conclusion: The therapeutic effect of the combination of Xiaoaiping Injection and chemotherapy on advanced esophageal cancer is obvious, and it can effectively improve the coagulation function, improve the quality of life, and be safe and reliable, so it's worth popularizing and application.