〔Abstract〕 Objective To analyze the interaction between voriconazole(VRC) and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR) based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring, so as to provide a basis for the development of individualized VRC combined with immunosuppressants. Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene polymorphism, respectively. And the concentration of immunosuppressants was detected at the same time. The relationship among CYP2C19 gene polymorphism, the concentration of VRC and immunosuppressant and ADR was analyzed. Results A total of 61 patients were enrolled in this study, and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1%(33/61) and 9.84%(6/61), respectively. The concentrations of VRC in patients with extensive metabolism(EMs), intermediate metabolism(IMs) and poor metabolism(PMs) were(4.44±3.46),(3.62±3.02) and(10.05±1.46) μg/ml(P<0.05), respectively. The concentration of tacrolimus after combined with VRC significantly increased compared to tacrolimus alone [(13.4±9.2) ng/mlvs(6.5±3.6) ng/ml;P=0.002], and the concentration of tacrolimus increased along with an increasing of VRC concentration. The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosuppressants [(3.81±3.48) μg/mlvs(5.84±3.71) μg/ml;P=0.032]. The concentration of VRC in patients with cyclosporine significantly decreased(P<0.01), while tacrolimus and mycophenolate mofetil had no significant effect on the concentration of VRC. 45.90%(28/61) of the patients had adverse reactions, the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR [(7.07±3.43) μg/mlvs(3.06±2.90) μg/ml;P<0.001]. And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype. Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC, and VRC has significant interaction with immunosuppressants such as tacrolimus. CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individualized treatment of tacrolimus and voriconazole, and is expected to minimize toxicity and improve treatment effects.