A strain of Staphylococcus simulans D14 (S. simulans D14) showed the highest nitrate reductase activity (NRA) of 4.52 mM NO 2 − /mg dry weight by the spectrophotometric method, which was screened from traditional Chinese sausage. When the UV mutagenesis time was 25 s, the positive mutation rate was the highest at 26.60%. The NRA of the obtained positive mutant UV-11 was 9.21 mM NO 2 − /mg dry weight, and the activity was found to be 1.04-fold higher than that of the original strain S. simulans D14. A Plackett-Burman design (PBD) was employed to screen the significant variables pH, KNO 3 (%) and incubation time (h), and response surface methodology (RSM) was used to optimize the significant variables using a Box-Behnken design (BBD). The results showed that the NRA of S. simulans UV-11 was 15.22 mM NO 2 − /mg dry weight under optimum conditions of 37 °C, pH 6.5, incubation time 15 h, KNO 3 0.045%, NaCl 5%, NaNO 2 0.015%, peptone 1%, and D-mannitol 1%, which increased by 65.2% compared with the unoptimized medium. Natural curing agents (containing 10 7 CFU/g S. simulans UV-11 under optimal conditions and 1.40% celery powder, T2) were added to the cured meat model. T2 produced significantly lighter and redder signals than the control group (C) and the addition of 150 ppm NaNO 2 group (T1). The thiobarbituric acid reactive substance (TBARS) of T2 was 2.30 mg malonaldehyde/kg product and residual nitrite of T2 was 7.1 ppm after 14 days of storage,which were lower than those groups of C and T1. Taking into account the results of cured meat models, S. simulans UV-11 could be selected as a potential starter culture for the processing of natural meat products.