The antiretroviral drug favipiravir inhibits RNA-dependent RNA polymerase. It has been developed for the treatment of novel coronavirus (SARS-CoV-2) infection disease (COVID-19). However, its pharmacokinetics in patients with COVID-19 is poorly understood. In this study, we measured favipiravir serum concentration by liquid chromatography-tandem mass spectrometry and conducted population pharmacokinetic (PPK) analysis. Thirty-nine patients were enrolled in the study: 33 were administered FPV 1600 mg twice-daily (BID) on the first day followed by 600 mg BID, and 6 were administered FPV 1800 mg BID on the first day followed by 800 mg or 600 mg BID. The median age was 68 years (range, 27-89 years), males were 31 (79.5%), median body surface area (BSA) was 1.72 m(2) (range, 1.11-2.2), and patients requiring invasive mechanical ventilation (IMV) at the start of favipiravir was 10 (25.6%). Two-hundred and four serum concentrations were available for pharmacokinetic analysis. A one-compartment model with first-order elimination was used to describe the pharmacokinetics. The estimated mean clearance/bioavailability (CL/F) and distribution volume/bioavailability (V/F) were 5.11 L/h and 41.6 L, respectively. Covariate analysis revealed that CL/F was significantly related to dosage, IMV use, and BSA. Simulation study showed that the 1600 mg/600 mg BID regimen was insufficient for the treatment of COVID-19 targeting EC50 (9.7microg/mL), especially in patients with larger BSA and/or IMV. A higher favipiravir dosage is required for COVID-19, but dose-dependent nonlinear pharmacokinetics may cause an unexpected significant pharmacokinetic change and drug toxicity. Further studies are warranted to explore the optimal favipiravir regimen.