Aldo-keto reductase family 1 member B10 (AKR1B10) is an NADPH-dependent reductase that is aberrantly expressed in hepatocellular carcinoma (HCC) and is involved in metabolic reprogramming, tumor cell proliferation, immune microenvironment regulation, and therapeutic resistance. This review summarizes the expression characteristics, oncogenic mechanisms, diagnostic and prognostic value, and clinical translational potential of AKR1B10 in HCC. Current evidence indicates that AKR1B10 is frequently elevated in HCC tissues and serum, and that its combination with alpha-fetoprotein (AFP) may improve the auxiliary detection of HCC, particularly in patients with AFP-negative disease. Mechanistically, AKR1B10 may promote HCC progression by stabilizing acetyl-CoA carboxylase α and enhancing lipid synthesis, disrupting retinoic acid metabolism, activating the PI3K/Akt pathway, and participating in autophagy, epigenetic regulation, immune microenvironment remodeling, and multiple drug-resistance networks. However, the associations of AKR1B10 with tumor invasion, metastasis, and patient outcomes remain controversial. In some studies of tumor tissues, high AKR1B10 expression has been associated with lower tumor stage, less vascular invasion, and better prognosis, whereas elevated serum levels and high transcriptomic expression in some public databases have been linked to greater tumor burden and poorer survival. These discrepancies may be attributable to differences in biospecimen type, tumor differentiation and disease stage, etiological background, treatment modalities, and intratumoral heterogeneity. Although AKR1B10 shows potential as an auxiliary biomarker and therapeutic target for HCC, its clinical application is limited by the lack of standardized detection protocols and high-quality prospective evidence. Future studies should focus on etiology- and stage-stratified multicenter prospective validation, establishment of standardized detection and risk-stratification systems, clarification of the stage-specific biological functions of AKR1B10, and development of highly selective inhibitors and biomarker-guided combination therapies to facilitate its translation from basic research to precision diagnosis and treatment.