Abstract Background The inner association of inflammation with voriconazole (VCZ) metabolism has not been fully investigated. This study further discussed the relationship between C-reactive protein (CRP) and voriconazole blood trough concentration, and provided reference for clinical rational use of voriconazole in the treatment of inflammatory diseases. Objective To investigate the influence of CRP on the trough concentration of voriconazole (VCZ) and provide reference for rational drug use in clinical practice. Methods The data of patients who used voriconazole in our hospital were analyzed retrospectively, and the plasma concentration of voriconazole was determined by High Performance Liquid Chromatography(HPLC). The effects of age, sex, liver function, kidney function and CRP on plasma concentration of voriconazole were analyzed, and the relationship between CRP and the plasma concentration of voriconazole was analyzed by using the ROC curve of the subjects. Results In total, 284 patients were included in the study. Gender, age and renal function had no obvious influence on the valley concentration of voriconazole.There was a significant correlation between Glutamyltranspeptidase (GTP) and voriconazole valley concentration (P = 0.00487). With the increase of CRP, the trough concentration of voriconazole also increased. In the ROC curve evaluation, the area under the diagnostic curve (AUC) with CRP value of the predictor is 0.7898 (95% CI = 0.7157 ~ 0.8639, P < 0.0001), and the corresponding optimal critical cut-off point was 37.7 mg/L, which indicated that when the CRP was 37.7 mg/L, the incidence of voriconazole blood trough concentration exceeding 5.0 mg/L was high. Conclusion The blood trough concentration of voriconazole is very different between human and human.. Inflammation is one of the factors affecting the concentration of voriconazole in blood. It can be predicted that the CRP value will be higher than 37.7 mg/L, and the blood concentration of voriconazole may be higher than 5.0 mg/L under the same loading dose. Therefore, it is suggested to pay attention to CRP in patients when voriconazole is used clinically. When it is higher than 37.7 mg/L, more attention should be paid to the blood trough concentration of voriconazole to avoid liver dysfunction and other more serious complications.