BACKGROUND Analyzing liver cancer incidence is essential for identifying trends and determining risk factors, which, in turn, guide strategies for prevention and treatment. By focusing on high-risk populations, such analyses enhance health outcomes and cancer risk management. METHODS A retrospective study was conducted using data from the Centers for Disease Control-Wide-ranging Online Data for Epidemiologic Research database (1999-2020) to evaluate liver cancer incidence trends in the United States (US) by age, gender, and race. RESULTS Demographic variations of liver cancer in the US from 1999 to 2020 were determined. A state-wise distribution of crude rates per 100,000 and incidence across the US during the same period was established. Based on age, gender, and race, the fluctuating trends in liver cancer incidence from 1999 to 2020 were also investigated. CONCLUSIONS This study shows state-wise variations in liver cancer incidence; however, crude rates per 100,000 remain relatively consistent across states. Over 22 years, liver cancer rates have increased, with the highest incidence found in men, White individuals, and those aged 65-74. Incidence increased for individuals over 45, but by the end of two decades, rates for ages 45-54 decreased while remaining high for ages ≥55. A more prominent upward trajectory was observed in men compared to women and in Whites compared to other races, underscoring the need for targeted prevention and control strategies.