Based on the early single factor test, quadratic regression orthogonal rotating combination design was applied. The whole gas production was taken as response value. Effects of four factors on anaerobic fermentation were studied. These four factors are the ratio of food garbage and cow dung, temperature, pH value and the ratio of inoculum and quality of fermentation. The mathematical mode about mixed fermentation of food garbage and cow dung was established, regression equation was optimized and analyzed, in addition, the optimal condition and interactive effects were exposed. The optimum technological conditions for the mixed-fermentation was as the followings: the ratio of food garbage and cow dung was 2.5, temperature was 37.5℃, the pH value was 7.0 and the ratio of inoculum volume and quality of fermentation was 4. The order of the influence of four factors on mixed-fermentation of food garbage and cow dung was as follows: the ratio of inoculum and quality of fermentation, temperature, the ratio of food garbage and cow dung, and pH value. The gas production of the optimum technological condition and the random experiment also showed no significant difference with the predictive value. The model fitted well.