Purpose The role of betel quid on the development of liver cirrhosis is unclear; we thus designed a community-based case-control study to evaluate the association between betel quid chewing and liver cirrhosis. Methods A total of 42 cases of liver cirrhosis and 165 matched controls were included for analysis. Questionnaires were administered to obtain histories of betel quid chewing, alcohol consumption, smoking, and family history of liver disease. Hepatitis B surface antigen and anti-hepatitis C antibody were also determined by immunoassay. Results Individuals with more betel quid chewing (more than 55 quid-years vs. less than 55 quid-years and never-chewers, matched odds ratio [OR m] = 2.2; 95% confidence interval [CI]: 1.0–5.0) had higher risks for liver cirrhosis. The combined effects on liver cirrhosis by betel quid chewing and the number of other risk factors, including hepatitis B virus (HBV) infection, smoking, and alcohol drinking, were also observed. When individuals with less betel quid chewing (less than 55 quid-years and never-chewers) and with no other risk factors used as a reference, betel quid chewers expressing greater betel quid chewing (more than 55 quid-years) and more risk factors of HBV infection, cigarette smoking, and habitual alcohol drinking expressed a greater risk of liver cirrhosis (OR m = 70.8; 95% CI: 4.0–1260.1). Conclusions Our results suggest that betel quid chewing may play an important role in the development of hepatic cirrhosis. Larger study and cohort studies would be necessary to provide further evidence regarding this finding.