Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer globally and stands as the third leading cause of cancer-related fatalities. Over the past few decades, non-viral factors contributing to HCC have become increasingly apparent, with non-alcoholic fatty liver disease (NAFLD) emerging as the most significant. NAFLD encompasses a spectrum ranging from simple liver fat accumulation in individuals without excessive alcohol consumption to non-alcoholic steatohepatitis (NASH), which may or may not involve cirrhosis. The Medline, Pubmed, Embase, NCBI, and Cochrane databases were searched for studies of patients with non-alcoholic fatty liver disease. Incidence, etiology, and management options were analyzed. As the field progresses, early indications of potentially reduced responsiveness to immunotherapy for NAFLD-related HCC highlight the need for more frequent and rigorous investigations into non-immune systemic treatments for this patient subgroup. Furthermore, it is crucial to conduct randomized controlled trials specifically assessing the effectiveness of immunotherapy in this population. Several considerations must be addressed in such studies, including the precise definition of NAFLD, metabolic-associated fatty liver disease, or NASH, the diversity within this group encompassing lean NAFLD, metabolic syndrome-related NAFLD, and other subtypes, as well as the influence of concurrent health conditions and medication profiles.