AIM: To predict voriconazole (VCZ)'s pharmacokinetics in patients with different degree of liver dysfunction. METHODS: The physiological based pharmacokinetics (PBPK) models were developed for VCZ based on drug's physico-chemical property and in-vitro data. Then liver dysfunction induced changes in physiological, anatomical parameter was integrated into the PBPK model. The clinical verified VCZ model was used to predict VCZ's PK in patients of different CYP2C19 genotype with different degree of liver dysfunction. RESULTS: The PBPK predicted the VCZ exposure in the patients with liver dysfunction with acceptable prediction error. CONCLUSION: The PBPK model developed here could evaluate the impact of liver dysfunction and CYP2C19 genotype on VCZ's pharmacokinetics and support individual dose adjustment of VCZ.