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Yang Zhao,1,* Jun Liu,2,* Zhengping Xiong,1 Shanzhi Gu,1 Xibin Xia2 1Department of Interventional Therapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China; 2Department of Radiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanzhi Gu, Department of Interventional Therapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China, Email 171761993@qq.com Xibin Xia, Department of Radiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China, Email zghnxxb@163.comObjective: This retrospective study aimed to investigate whether pre-treatment inflammatory biomarkers, including the prognostic nutritional index (PNI), monocyte-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and platelet-lymphocyte ratio (PLR), could predict treatment response and prognosis in patients with hepatocellular carcinoma (HCC) receiving hepatic arterial infusion chemotherapy (HAIC) with the oxaliplatin, leucovorin, and fluorouracil (FOLFOX) regimen.Methods: Based on the cut-off values identified using the receiver-operating characteristic (ROC) curve, 124 patients with HCC who received HAIC with the FOLFOX regimen were divided into low- and high-score MLR, PLR, PNI, and SII groups. Univariate and multivariate regression analyses were performed to identify independent predictors of treatment response and progression-free survival (PFS).Results: The cut-off values were 0.569 for MLR (area under the curve [AUC]: 0.621), 177.01 for PLR (AUC: 0.554), 713.05 for SII (AUC: 0.570), and 46.85 for PNI (AUC: 0.665). Multivariate Cox regression analysis revealed that the modified albumin-bilirubin (mALBI) grade (hazard ratio [HR]: 2.027; P=0.032), high MLR (HR: 7.250; P=0.002), and low PNI (HR: 0.296; P=0.003) were independent predictors of HAIC non-response, with an AUC value of 0.746 (95% CI: 0.658– 0.833). A high MLR (HR: 1.714, 95% CI: 1.086– 2.704, P=0.021) was also an independent predictor of PFS. Kaplan–Meier analysis showed that the patients with a high MLR had shorter PFS than those with a low MLR (median PFS: 6 vs 10 months, P=0.011).Conclusion: The pre-treatment MLR and PNI were predictors of non-response in patients with HCC receiving HAIC with the FOLFOX regimen. The MLR also was an independent predictor of PFS.Keywords: hepatocellular carcinoma, inflammatory biomarkers, treatment response, hepatic arterial infusion chemotherapy, progression-free survival