Introduction: To investigate the clinical effect of total hilar resection and reconstruction in patients with hepatobiliary carcinoma and its influence on inflammatory factors and hemorheology. Materials and methods: A total of 64 patients with hepatobiliary carcinoma admitted to the hospital from January 2019 to February 2021 were randomly divided into two groups, with 32 cases in each group. The control group received palliative tumor resection and internal drainage to reduce yellow surgery, while the test group received total hilar resection and reconstruction. The clinical treatment efect, surgical indexes, inflammatory factor levels and hemorheology indexes were compared between the two groups. Results: Compared with the control group, the clinical treatment effect was better in the test group (P<0.05), and the indexes of intraoperative blood loss, operation time and hospital stay were more excellent in the test group (P<0.05). Also, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), hypersensitive C-reactive protein (HS-CRP) and other inflammatory factors were lower at 3, 5 and 7 days after operation (P<0.05). The hemorheology indexes such as blood viscosity, low shear viscosity, medium shear viscosity and high shear viscosity, erythrocyte specific volume and erythrocyte aggregation index in the test group were better than those in the control group (P<0.05). Conclusion: The application of total hilar resection and reconstruction in the surgical treatment of patients with hepatobiliary carcinoma can effectively optimize the surgical indexes and hemorheology indexes, reduce the inflammatory factor levels, and improve the prognosis, with obvious effects.