A new method for sulfur dioxide determination based on high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS/MS) was established to solve the problems of significant matrix interference and difficulty in accurately measuring sulfur dioxide content in complex-matrix foods. Experimental parameters, such as the optimal target analyte for sulfur dioxide detection and gas flow rate in the collision cell, were determined through testing. Additionally, the experimental conditions, including the mass concentration of formaldehyde absorption solution, injection volume, mobile phase pH value and concentration, and mobile phase flow rate, were optimized. The results showed a strong linear relationship between the analyte response signals and sulfur dioxide concentration over the range of 0.0~20.0 mg•L-1 (R2= 0.999 9). The background equivalent concentration (BEC) was 7.4 μg•L-1, detection limit was 3 mg•kg-1, and quantification limit was 9 mg•kg-1. This method can accurately determine the amount of residual sulfur dioxide in wine, pickled vegetables, and dried fruits. The recovery rates of spiked samples with different concentrations using yeast extract as the matrix ranged from 93.0% to 105.9%, with relative standard deviations (RSD) below 5%. This method can overcome complex-matrix interference and shorten the inspection time. Enhancing the applicability, accuracy, and sensitivity of this method can facilitate the precise determination of sulfur dioxide residues in food, thereby providing efficient and convenient technical support for routine supervision and helping to build a more comprehensive food safety assurance system.