In the study, the fermentation process of Scutellaria baicalensis residues fermented by Lactobacillus plantarum was studied and the optimal process conditions were optimized by response surface methodology. Five fermentation conditions including substrate water content, fermentation temperature, fermentation time, initial pH value and inoculation amount were tested by single factor experiment. Plackett-Burman climbing experiment was designed to screen the key factors based on the best single factor experiment. The Box-Behnken experiment was used to design the key factor of fermentation and optimize the response surface method. The optimized fermentation conditions were validated and analyzed. The results showed that among five factors, the water content of Scutellaria baicalensis residues, initial pH value and fermentation temperature were the key factors affecting the fermentation process. The optimal conditions for the number of lactic acid bacteria in fermented Scutellaria baicalensis residues were obtained through optimization of Box-Behnken response surface experiment. The optimum fermentation conditions were as follows, the maximum number of live lactic acid bacteria was 8.32×108 CFU/g while the water content of Scutellaria baicalensis residues was 63%, initial pH value was 6.3, fermentation temperature was 33 ℃. The experiment indicates that optimal fermentation process conditions for Lactobacillus plantarum fermented Scutellaria baicalensis residues are optimized by response surface methodology. [ABSTRACT FROM AUTHOR]