Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related deaths, according to the 2020 Global Cancer Statistics [1]. Despite high incidence and mortality rates of liver cancer in China, comprehensive treatments, including the addition of targeted therapy and/or immunotherapy-based systemic treatment to local therapies, such as liver resection, local ablation, and intra-arterial therapies, have been adopted in real-life practice and are benefiting an increasing number of patients [2]. In recent years, the application of immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) / programmed death ligand 1 (PD-L1) inhibitors, for the systemic treatment of HCC has significantly improved clinical outcomes. The objective response rate to immunotherapy combined with other treatments for advanced hepatocellular carcinoma ranges from 15 to 46 %. However, there is considerable variation in treatment efficacy and prognosis among patients, and the potential for severe adverse reactions poses ongoing challenges in clinical practice. Given that the prediction of target efficacy serves as a biological biomarker for immunotherapy sensitivity, numerous clinical studies and practices have revealed that the expression level of PD-L1 in tumor cells is not correlated with treatment response [3]. Therefore, the search for new biomarkers and the identification of advantageous populations of immune therapy for HCC represent pressing objectives in precision personalized treatment. This endeavor is critical not only for enhancing overall patient prognosis but also constitutes a prominent and challenging domain in immunotherapy research. Nneutrophil-to-lymphocyte ratio (NLR) is a novel predictive indicator for immunotherapy sensitivity, besides tumor mutation burden (TMB), mismatch repair genes (MMR), and microsatellite instability (MSI). In addition to tumor cells, the tumor microenvironment comprises various cell types, including immune cells (T cells, NK cells, macrophages, and neutrophils, among others), fibroblasts, various soluble cytokines, and the extracellular matrix [4], [5]. As NLR is an inflammatory marker, its expression level is related to the efficacy and prognosis of immunotherapy in various cancer patients [6], [7]. Although serum NLR has garnered significant attention because of its simplicity, convenience, and low cost, as it primarily relies on routine tests and serves as an auxiliary reference indicator for predicting treatment efficacy, NLR within tumor tissues better reflects local immune responses. Therefore, building upon the analysis of NLR within HCC tissues and its correlation with immunotherapy efficacy, this study further explores the underlying mechanisms and aims to identify more convenient and effective molecular markers.