<p>Hepatocellular carcinoma remains one of the leading causes of cancer-related mortality worldwide, yet the disease manifests and progresses differently between sexes. Significant disparities in risk factors, diagnosis, and therapeutic outcomes are shaped by a combination of biological differences and sociocultural influences. Males face a significantly higher risk of developing HCC, primarily due to greater exposure to key risk factors such as chronic hepatitis B and C infections, excessive alcohol consumption, and metabolic disorders. In contrast, females generally exhibit better prognoses, attributed to the protective effects of estrogen and stronger immune responses. However, despite these advantages, females often experience delays in diagnosis and encounter barriers to accessing optimal treatment options. This narrative review explores the sex- and gender-based disparities in HCC, highlighting their impact on disease progression, diagnosis, and treatment effectiveness. Understanding these differences is crucial for improving patient outcomes and advancing personalized therapeutic approaches for HCC management.</p>