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The study aimed to investigate the independent effects of serum branched-chain and aromatic amino acid levels on hepatocellular carcinoma (HCC) development. This multicenter retrospective study included patients with chronic liver disease (CLD) from two institutions in Japan. Amino acid imbalance was assessed using BCAA and tyrosine levels. Factors associated with the development of HCC and mortality were assessed using Fine-Gray competing risk and Cox proportional hazards regression models, respectively. Among 563 patients, the median age was 67 years, and 51% were male. During a median follow-up period of 3.5 years, 14% (n = 80) of the patients developed HCC and 23% (n = 130) died. Given mortality as a competing risk, multivariable analysis showed that the serum tyrosine level (sub-distribution hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00-1.02) was an independent risk factor for the development of HCC. Similarly, using the development of HCC as a time-dependent covariate, the serum tyrosine level (HR, 1.01; 95% CI, 1.01-1.02) and development of HCC (HR 2.91; 95% CI 1.75-4.81) were independent risk factors for mortality. The serum tyrosine level is an independent risk factor for the development of HCC and mortality in patients with CLD.