Background <p>Inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), serve as crucial indicators of tumor-immune system interactions and reflect the tumor immune microenvironment. Although the prognostic significance of baseline inflammatory indices in oncology is well-recognized, the correlation between the temporal variations of these biomarkers during transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) and therapeutic response warrants further investigation.</p> Methods <p>This retrospective cohort study analyzed clinical data from 157 HCC patients undergoing TACE between 2021 and 2023. Preoperative NLR, postoperative NLR, and three-month postoperative NLR values were collected to assess tumor response and prognosis. Predictive factors for the disease control rate at three months were identified using logistic regression. Subsequently, patients were stratified based on the optimal cut-off value derived from ROC curve analysis, followed by survival and prognostic analyses.</p> Results <p>The longitudinal change in NLR from preoperative to three-month follow-up, as opposed to the baseline NLR value alone, emerged as a significant predictor of disease control. And an elevated NLR trajectory was robustly associated with tumor progression. Furthermore, increased NLR changes were correlated with inferior overall survival outcomes (median survival: 26.326 vs. 20.294 months, <i>p</i> = 0.005).</p> Conclusion <p>The dynamic NLR changes demonstrate significant correlation with therapeutic outcomes in HCC patients receiving TACE. This biomarker exhibits potential as a prognostic indicator for identifying TACE-responsive patients, thereby offering valuable guidance for subsequent therapeutic decision-making.</p>