Abstract: Salmonella is one of the main foodborne pathogens causing foodborne diseases for human beings. How to effectively control the Salmonella contamination is an urgent question in the field of food safety. In this study, hydroxypropyl-β-Cyclodextrin (HP-β-CD) and curcumin (CUR) were incubated to construct the inclusion complex, which was used as a photosensitizer. Then the CUR-HP-β-CD mediated photodynamic inactivation technology (PDI) on Salmonella Typhimurium ATCC14028 in food samples was determined under light-activated, and the mechanisms of the antibacterial activities were studied. Using 40% of ethanol and 2:1 (n/n) of HP-β-CD, the highest CUR inclusion rate (60.08%) was observed at 45 ℃ for 4 h. The water solubility of the inclusion complex was significantly improved to 3.98×10³ μg/mL. The results indicated that with an initial cell concentration of 10⁶ CFU/mL and 20 µg/mL of the inclusion complex (calculated as CUR), the survival of Salmonella Typhimurium had a reduction of 3.73 lg (CFU/mL) and a 47.92% to 64.40% of antibacterial activities against drug-resistant Salmonella were observed under the LED (450 nm) irradiation for 40 minutes. This CUR-HP-β-CD mediated PDI technology can also be used to control the Salmonella contamination in ready-to-eat lettuce samples. After the PDI treatment, higher levels of reactive oxygen species was tested and the cellular contents were significantly reduced, suggesting that CUR-HP-β-CD mediated PDI presented antibacterial activities mainly by disrupting the cell membrane structures of Salmonella. This study aims to provide the PDI technology in the field of food safety, and gives strong theoretical and technical supports for the prevention and control of contamination by Salmonella and other foodborne pathogens in food industry.