Objective To analyze the expression level of osteosarcoma proto-oncogene B (FOSB) and secretory phosphoprotein 1 (SPP1) in liver cancer tissues of patients with advanced liver cancer treated by transcatheter arterial chemoembolization.Methods A retrospective analysis was performed on 115 patients with advanced liver cancer diagnosed and treated in the First Affiliated Hospital of Xi ′an Medical University in Shanxi Province from January 2016 to October 2017. According to the level of FOSB and SPP1 gene expression, they were divided into 52 cases of FOSB high expression group, 63 cases of FOSB low expression group, 89 cases of SPP1 high expression group and 26 cases of SPP1 low expression group. To analyze the relationship between the expression of FOSB and SPP1 and the clinicopathological characteristics of patients with advanced hepatocellular carcinoma, the patients included in the study were followed up for 60 months. Logistic risk regression model was used to analyze the risk factors affecting the survival period of patients. Kaplan-Meier survival curve was used to analyze the relationship between the expression level of FOSB and SPP1 and the survival and prognosis of patients. Results The expression level of FOSB mRNA in peripheral blood mononuclear cells of patients with liver cancer was significantly lower than that of the healthy control group, and the expression level of SPP1 mRNA was significantly higher than that of the healthy control group (P＜0.05). The expression of FOSB and SPP1 was significantly different in tumor size, Child-Pugh grade, lymph node metastasis and BCLC stage in patients with advanced hepatocellular carcinoma (P＜0.05). The results of univariate analysis showed that there were statistically significant differences between the survival group and the death group in tumor size, Child-Pugh grade, lymph node metastasis, BCLC stage,FOSB and SPP1 expression (P＜0.05). Tumor size, Child-Pugh grade, lymph node metastasis, BCLC stage, low expression of FOSB and high expression of SPP1 were all independent risk factors for survival of patients with advanced hepatocellular carcinoma (P＜0.05). The follow-up time was 60 months. The survival rate of patients was 17.39% (20/115). The median survival time of FOSB high expression group was 39.7 months, which was significantly higher than 19.3 months of FOSB low expression group (P＜0.05). And the median survival time of the low-expression SPP1 group was 48 months. It was significantly higher than that in SPP1 high expression group at 37.5 months (P＜0.05). Conclusion The expression level of FOSB is significantly down-regulated and the expression of SPP1 is up-regulated in patients with advanced liver cancer, which has certain value in predicting the survival period of patients with advanced liver cancer treated by transcatheter arterial chemoembolization. FOSB and SPP1 are expected to become potential indicators to evaluate the prognosis of patients undergoing interventional therapy, and can predict or evaluate the survival of patients with liver cancer after surgery in cooperation with clinical indicators such as Child-Pugh grade, lymph node metastasis, BCLC stage