BackgroundInflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery. MethodsA total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson's chi 2 test or Fisher's exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model. ResultsThe patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model. ConclusionInflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.