Fresh-cut fruits and vegetables are the main sources of foodborne illness outbreaks with implicated pathogens such as Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes. This study aimed at investigating the influence of two key parameters (concentration of curcumin and illumination time) on the effects of curcumin-based photodynamic sterilization on the preservation of fresh-cut Hami melons. The results indicated that illumination with 50 &mu / mol/L curcumin for 60 min using a blue LED lamp reduced the total aerobic microorganism count by ~1.8 log CFU/g in fresh-cut Hami melons. Besides this, the effects of photodynamic sterilization on the soluble solids content, color, water content, firmness, and sensory indices of the fresh-cut Hami melons were also evaluated. Compared to the control group, photodynamic sterilization can effectively delay the browning rate and maintain the luminosity, firmness, water content, and soluble solids content of fresh-cut Hami melon. The sensory quality was indeed preserved well after 9 days of storage in a fridge. These results showed that photodynamic sterilization is an effective and promising technology to prolong the shelf life of fresh-cut Hami melons.