Objective: To evaluate the predictive value of secreted phosphoprotein 1 (SPP1) gene expression for postoperative survival in patients with advanced liver cancer undergoing hepatic artery interventional chemoembolization treatment. Method: Bioinformatics methods, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were used to identify genes related to survival prognosis in hepatocellular carcinoma (HCC) patients. A retrospective analysis of 115 advanced liver cancer patients treated between January 2016 and October 2017 was conducted. Patients were categorized into SPP1 high-expression (n = 89) and low-expression groups (n = 26). Additionally, 115 healthy individuals served as the control group. The relationship between SPP1 expression and clinical pathological features was analyzed. A 60-month follow-up and logistic regression analysis identified risk factors affecting survival. Results: SPP1 mRNA expression was significantly higher in liver cancer patients compared to healthy controls (P < 0.05). SPP1 expression levels were significantly associated with tumor size, Child-Pugh grading, lymph node metastasis, and BCLC staging (P < 0.05). High SPP1 expression, along with tumor size, Child-Pugh grading, lymph node metastasis, and BCLC staging, were independent risk factors for survival (P < 0.05). The 60-month survival rate was 17.39%, with a median survival of 40 months in the low-expression group versus 18 months in the high-expression group (P < 0.05). Conclusion: SPP1 expression is significantly upregulated in advanced liver cancer patients and has predictive value for postoperative survival following hepatic artery chemoembolization treatment. SPP1, combined with clinical indicators such as tumor size, Child-Pugh grading, lymph node metastasis, and BCLC staging, may serve as a prognostic biomarker for interventional treatment outcomes.