Abstract: OBJECTIVE To establish an internal quality control method for therapeutic drug monitoring of voriconazole by HPLC-MS/MS and evaluate it by Westgard multi-rule theory. METHODS Voriconazole as analyte and fluconazole as internal standard were weighed and dissolved in methanol. Then they were added into the blank plasma matrix according to the plasma treatment method to prepare quality control products with low, medium and high concentration(80, 5 000, 8 000 ng·mL^-1). HPLC-MS/MS was applied to determine the concentrations of 36 groups of different quality control products from December 2020. The control charts of Levey-Jennings quality and Z-score were generated by Excel, and Westgard multi-rules were also used for quality assessment. RESULTS The intra-day and inter-day RSDs of low, medium and high concentration of voriconazole quality control products were 4.9%-5.3%, 6.0%-7.1%, respectively. While the extraction recovery rates of internal standard and voriconazole were 110%-112%, 98%-112%, respectively. This met the requirements of Chinese Pharmacopoeia for the detection of biological samples. The results of Levey-Jennings quality control chart and Z-score quality control chart indicated that the concentration detection results of the 36 groups of quality control plasma samples were all within the controllable range. CONCLUSION The establishment of internal quality control system for therapeutic drug monitoring of voriconazole can effectively improve the accuracy of blood drug concentration monitoring, and provide more accurate clinical individualized medication.