Objective: To establish a rapid qualitative and quantitative analysis method, HPLC-quadrupole-time-of-flight mass spectrometry was used to determine the illegal addition of 19 antidepressants in healthy food. Methods: The samples were extracted by methanol with ultrasonic extraction procedure and then separated on a reversed-phase C₁₈ column, with acetonitrile and 0.1% formic acid aqueous as the mobile phases in gradient elution mode. The target compounds were detected in electrospray positive ion, and the data were matched with the established database of precursor ion and secondary fragment accurate mass. Results: The linear range of the 19 compounds was 5~100 μg/L, and the correlation coefficient was 0.988 7~0.999 9, with the detection limit of 0.2~2.0 μg/kg. The average recoveries of the 19 antidepressants ranged from 81.2% to 98.6%, and the relative standard deviation was less than 6.7%. Conclusion: The established method is suitable for rapid screening qualitative and quantitative analysis of illegally added antidepressant drugs in healthy food.