<p>Cancer-related fatigue (CRF) is a multifaceted and subjective phenomenon that significantly impacts patients on physical, emotional, and mental levels. This study aims to identify specific subtypes of Cancer-related fatigue (CRF) in patients with Hepatocellular Carcinoma (HCC) and to explore the factors influencing each subtype. This cross-sectional study enrolled 220 participants from a tertiary cancer hospital. Latent Profile Analysis (LPA) and multinomial logistic regression were conducted to identify distinct fatigue profiles and to explore the influencing factors for different categories of CRF among the patients. The analysis revealed three potential categories of CRF severity: Physical balance -Low fatigue (20.1%); Physical imbalance -Moderate fatigue (69.6%); and Physical prominent -High fatigue (10.2%). It was found that the severe insomnia the greater the probability of patients belonging to the Physical prominent -High fatigue (OR = 1.299, 95%CI: 1.188–1.419). Has partner (OR = 5.171, 95%CI: 1.739–15.377), the severe financial stress (OR = 2.570, 95%CI: 1.209–5.463) and the moderate ISI (OR = 1.212, 95%CI: 1.136–1.292) were associated with the Physical imbalance - Moderate fatigue group. Protective factors for the Physical balance - Low fatigue group included higher scores in the physical activity Index (OR = 0.930, 95%CI: 0.870–0.995), Hope Index (OR = 0.647, 95%CI: 0.552–0.758), General self-efficacy (OR = 0.874, 95%CI: 0.793–0.965), Body Mass Index (OR = 0.799, 95%CI: 0.552–0.758), and Child-Pugh A classification (OR = 0.310, 95%CI: 0.119–0.808). CRF in patients with HCC demonstrates significant heterogeneity. It is conducive to the clinical identification of CRF risk characteristics and the design of personalized intervention measures.</p>