Prescribing antimicrobial therapy in critically ill patients is challenging given lack of standard recommendation. Herein, a pharmacokinetic study of intravenous posaconazole was conducted to confirm plasma and tissue concentrations in a 37-year-old patient with invasive Aspergillus terreus infection coincided with renal and hepatic impairment. After dosing adjustment to 300mg every 48 hours, posaconazole exposure using area under the concentration-time curve (AUC) and average concentration (Cavg) reached the target recommendation. However, no significant accumulation of tissue posaconazole was found. Moreover, hyperbilirubinemia may have an influence on posaconazole pharmacokinetics that further studies are needed to explain this phenomenon.