The production of halophilic thermostable protease by Haloferax lucentensis VKMM 007 was optimized using a statistical approach. In accordance with factorial design, soluble starch, gelatin, KCl and MgSO4 were selected among 27 variables tested. Next, a second-order quadratic model was estimated and optimal medium concentrations were determined based on quadratic regression equation generated by model. These were 5.14 g L(-1) of KCl, 6.57 g L(-1)of MgSO4, 9.05 g L(-1)of gelatin and 5.27 g L(-1)of soluble starch in high salts media supplemented with 0.5% (w/v) of beef extract and peptone, respectively. In these optimal conditions, the obtained protease concentration of 6.80 U mL(-1) was in agreement with the predicted protease concentration and was further improved to 7.02 U mL(-1) by increasing the concentration of NaCl in the medium to 25% (w/v). An overall 4.0-fold increase in protease production was achieved in the optimized medium compared to activity obtained in initial medium.