Optimal medium was used to improve the production of keratinase by Bacillus licheniformis ZJUEL31410, which has a promising application in the transformation of feather into soluble protein. The results of single factor design revealed that the concentration of feather at 20 g/l and the initial pH at value 8 was the best for the production of keratinase and the degradation of feather. Ammonia salt and nitrate salt strongly restricted the production of keratinase and the degradation of feather. Result of Box-Behnken design (BBD) experiment which was used to optimize concentrations of glucose, corn steep flour and K2HPO4 for further improvement of keratinase productivity showed that the optimal medium was composed of glucose (20 g/l), corn steep flour (7.5 g/l), K2HPO4 (1 g/l) and feather (20 g/l). The result of submerged batch cultivation of B. licheniformis ZJUEL31410 in the 5 L fermentor indicated that the optimal medium had the highest keratinase and the degree of feather degradation (DFD) at 54.9 U/ml and 72.4%; both were 5 times more than the basal medium. The degradation of feather was verified by the analysis of scanning electron microscopy (SEM). This study provides a foundation for the production of keratinase and the conversion of feather to soluble protein through submerged fermentation process by B. licheniformis ZJUEL31410.