Background: Liver cancer poses a significant global health challenge. Smoking and alcohol consumption are major risk factors for liver cancer.

Methods: We analyzed data from the Global Burden of Disease (GBD) Study 2021. First, numbers and age-standardized rates of deaths and disability-adjusted life years (DALYs) were assessed globally and by sub-types in 2021. Furthermore, the temporal trend of the disease burden was explored by the linear regression model from 1990 to 2019. Based on the EAPC values, we conducted a hierarchical cluster analysis to categorize the 54 GBD regions into four groups. To explore potential associations between the EAPCs and socioeconomic factors, we employed the Spearman correlation analysis to evaluate the correlation between EAPCs and ASRs, as well as Human Development Index (HDI) scores. Finally, frontier analysis was used to visually demonstrate the potential for burden reduction in each country or region based on their development levels. All analyses were conducted using R software.

Results: From 1990 to 2021, the burden of liver cancer attributed to alcohol consumption increased significantly, whereas age-standardized rates (ASRs) remained relatively stable compared to those associated with smoking.In 2021, the number of deaths and disability-adjusted life years (DALYs) due to smoking-related liver cancer were 53,054 (95% uncertainty interval [UI]: 18,268–88,111) and 1,482,896 (95% UI: 505,000–2,478,906), respectively. The corresponding age-standardized rates (ASRs) were 0.61 per 100,000 population (95% UI: 0.21–1.01) for mortality and 16.9 per 100,000 (95% UI: 5.76–28.26) for DALYs. The estimated annual percentage changes (EAPCs) for these ASRs were − 0.84 (95% confidence interval [CI]: -0.96 to -0.73) for mortality and − 1.12 (95% CI: -1.24 to -1.01) for DALYs.Conversely, in 2021, deaths and DALYs attributable to alcohol-related liver cancer totaled 93,807 (95% UI: 77,476–113,542) and 2,385,090 (95% UI: 1,949,109–2,911,783), respectively. The corresponding ASRs were 1.08 per 100,000 (95% UI: 0.89–1.30) for mortality and 27.2 per 100,000 (95% UI: 22.25–33.1) for DALYs. The EAPCs were 0.26 (95% CI: 0.19–0.32) for mortality and 0.04 (95% CI: -0.03 to 0.10) for DALYs. Males, middle-aged, and older adults were high-risk populations, and middle socio-demographic index (SDI) regions were high-risk areas. The Western Pacific had the highest ASDR for smoking-related liver cancer, while East Asia recorded the highest ASDAR. For alcohol-related liver cancer, the Commonwealth High-Income region exhibited the highest ASDR, whereas Australasia had the highest ASDAR. Andean Latin America had the lowest ASRs for both smoking- and alcohol-related liver cancer. Notably, Mongolia had the highest ASRs for liver cancer attributed to both smoking and alcohol consumption, with values hundreds of times greater than those in the country with the lowest burden, Morocco.

Conclusion: Although the ASRs of smoking-related liver cancer have continued to decline, the absolute number of cases remains high, and the burden of alcohol-related liver cancer continues to rise. Consequently, the overall disease burden associated with smoking and alcohol consumption remains significant, highlighting the urgent need for more effective risk factor control strategies. Furthermore, the establishment of accurate and efficient screening systems, as well as specialized cancer treatment centers, is imperative—particularly for high-risk populations, such as middle-aged and elderly men, and for high-risk regions classified as High and Middle SDI areas.