Objective:To retrospectively analyze the clinical efficacy, safety and the main factors affecting the prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer.Methods:Fifty-five cases with advanced primary liver cancer who received anlotinib hydrochloride were enrolled. The baseline data of the patients, such as prothrombin time, total bilirubin, albumin, Child-Pugh score, procalcitonin, alpha fetoprotein, extrahepatic metastasis, cirrhosis, portal hypertension, whether or not combined surgery, pathological staging, etc before treatment were recorded. Hematological and imaging results of the patients were reviewed. Adverse events that appeared in patients at any time until the end of follow-up or loss- to- follow-up or death were recorded. The survival curve was plotted by Kaplan-Meier method, and the difference of survival time between groups was examined by log-rank test. Cox regression model of single and multiple factor were used to analyze the factors affecting the prognosis.Results:As of the last follow-up, 2 patients were lost-to-follow-up, 30 died, and 23 survived. The median survival time was 6.5 months (196 days). Grade 3 or higher adverse events included hypertension (12.73%), leukopenia (3.64%), absolute neutropenia (1.82%), thrombocytopenia (9.09%), fatigue (3.64%), anemia (1.82%), and diarrhea (1.82%). Adverse events were effectively controlled. One case had fatal ruptured esophageal varices, which were not medically related. Multivariate Cox regression analysis showed that total bilirubin ( HR = 0.247, P = 0.003), albumin ( HR = 0.279, P = 0.003) and procalcitonin ( HR = 0.105, P = 0.012) were independent factors affecting the prognosis of advanced HCC. Conclusion:Anlotinib hydrochloride therapy is safe, effective and well tolerated in patients with advanced liver cancer, and total bilirubin, albumin, and procalcitonin are independent factors that affect the prognosis of patients with advanced liver cancer.