Abstract: The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θ_CL·(WT/60)^θ_WT·θ_CYP·e^η_CL (if CYP2C9^*1/^*1, θ_CYP = 1; if ^*1/^*3, θ_CYP = 0.708); EC₅₀ = θ_EC50·θ_VKOR·e^η_EC50 (if VKORC1- 1639AA, θ_VKOR = 1; if GA, θ_VKOR = 2.01); V = θ_V; K_E0 = θ_KE0; E_max = θ_Emax; E₀ = θ_E0·e^η_E0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.