Objective? To investigate the efficacy of Somatostatin combined with Pantoprazole in the treatment of patients with acute non-variceal upper gastrointestinal bleeding (ANVUGIB) and its effects on coagulation function and hemorheology indexes, in order to find more effective treatment options in the clinic. Methods? According to the random number table method, 102 ANVUGIB patients admitted to Qingyang Hospital of Jiangyin from September 2020 to September 2021 were divided into two groups, with 50 cases in each group. The two groups of patients were given routine symptomatic treatment such as anti-infection, supplementing blood volume, maintaining acid-base balance, etc. At the same time, patients in the control group were treated with Pantoprazole, on this basis, the patients in the observation group were treated with Somatostatin, both groups were treated for 3 consecutive days. The clinical efficacy, hemostasis time, hemoglobin (Hb) reduction degree, hospitalization time, coagulation function and hemorheology indexes before and after treatment, and adverse reactions during treatment were compared between the two groups. Results? The total clinical effective rates of the observation group was significantly higher than the control group; the hemostatic time and hospitalization time of the observation group were significantly shorter than those of the control group; the Hb reduction degree in the observation group was significantly lower than that in the control group; compared with before treatment, the plasma activated partial thromboplastin time (APTT) and prothrombin time (PT) of the two groups of patients after treatment significantly shortened, and the observation group was significantly shorter than the control group; plasma D-dimer (D-D) levels in both groups significantly decreased, and the observation group was significantly lower than the control group; the levels of plasma fibrinogen (FIB), whole blood high shear viscosity (HSV), low shear viscosity (LSV) and plasma viscosity (PSV) in the two groups significantly increased, and the observation group was significantly higher than the control group (allP<0.05); there was no significant difference in the total incidence of adverse reactions between the two groups of patients (P>0.05). Conclusion? The application of Somatostatin combined with Pantoprazole in the treatment of ANVUGIB can effectively relieve the clinical symptoms of patients, improve the clinical efficacy, improve the coagulation function and hemorheology of patients, and has high safety.