For a study, researchers sought to conduct a meta-analysis to investigate the role aspirin plays in developing HCC. They searched for this information in PubMed and EMBASE until September 2021. The outcomes showed that a total of 18 studies were included in the analysis (16 cohort and 2 case-control). Aspirin users had a reduced risk of developing hepatocellular carcinoma (HCC) compared to those who did not use the medication [adjusted odds ratio (OR), 0.54; 95% CI: 0.44-0.66]. Stratified research revealed that aspirin lowered the chance of developing head and neck cancer in both Western and Asian populations (OR, 0.59 vs. 0.67). In addition, aspirin has been shown to reduce the risk of HCC in patients who had previously been infected with the hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and the hepatitis C virus (OR, 0.41; 95% CI: 0.23-0.73). Both patients who already had chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and the general population might benefit from taking aspirin (OR, 0.65; 95% CI: 0.54-0.79). In addition, the results of the aspirin prevention of liver cancer study were significantly affected by the presence of confounding factors both before (OR, 0.28; 9%5 CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) correction was made. Additional research has demonstrated that those in the long duration group do not experience superior effects in preventing HCC than those in the shorter period group (OR, 0.62 vs. 0.63). The use of aspirin was not shown to increase the incidence of bleeding in patients with HCC, according to an additional meta-analysis that included 3 separate studies (OR, 1.19; 95% CI: 0.87-1.64). According to the meta-analysis’s outcomes, regular aspirin usage was associated with a reduced likelihood of developing liver cancer.