Sodium hypochlorite (NaClO) is widely used as a sanitizer to maintain microbial safety of lettuce; however, NaClO treatment is insufficient on pathogen reduction due to its high instability for an extended storage time. Hypobromous acid (HOBr) as another sanitizer, relatively stable in processing conditions, was applied to lettuce. The numbers of total aerobic bacteria, Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus were evaluated on lettuce treated with NaClO and HOBr. The population of 4 selected bacteria on lettuce reduced more than 2.5 log CFU/g. Bactericidal effect maintained for 10 days in combined treatment with 100 mg/L NaClO followed by 200 mg/L HOBr, while the population of the bacteria without HOBr treatment increased. Combined treatment on lettuce can give synergistic effect on reducing microbial population. Residual bromine was not detected on the lettuce treated with HOBr after washed with water for 30 s, indicating that bromine was effectively washed away.