Oyster mushrooms are used as raw materials for sauce because of their enhanced nutritious and sensory flavour. The study was aimed to select the optimal parameters of moromi fermentation of oyster mushrooms sauce. Optimizing moromi fermentation from oyster mushrooms by response surface method (RSM) was conducted with 3 factors including salt concentration (15-25% w/v), the brine ratio [150-250% (compared to raw materials, v/w)] and fermentation time (50-70 days). The central composite design used for optimizing the effect of salt concentration, amount of brine and fermentation time showed that the parameters were in agreement with the quadratic regression models well with R2>0.95. Based on the response surface plots, the optimal parameters of moromi fermentation were salt concentration 20% (w/v), brine ratio 190% (compared to raw materials, v/w) and 60 days of fermentation time. In the optimized condition, the chemical composition (reducing sugar, amino protein, total acids) and the bioactive compounds (β-glucan, total phenolic, total flavonoid) (per kg of dry matter) of fermentation sauce were 258.94 g, 204.76 g, 99.06 g, 86.57 g, 108.32 mg TAE and 93.78 mg QE, respectively.