Liver cancer (LCa) is the fifth and eighth leading cause of cancer death for men and women, respectively. However, despite improvements in treatment strategies and options, it has limited therapeutic options. Worldwide, the prevalence of LCa varies widely. Various factors are associated with the development of LCa, and its incidence, morbidity, and mortality rates differ due to disparities that are multifactorial and complex, including genetic and geographic factors. The frequency of LCa varies by race/ethnicity, age and sex and relates to viral infections, lifestyle, nutrition, obesity, and health. In addition, various molecular factors, including cytokines, hormones, apoptosis, and mutations, are involved in disparities in the progression and mortality of LCa. Here, we provide an overall perspective on LCa by presenting available information on these associated factors and discussing their importance in its disproportionate incidences and clinical outcomes.