Chicken manure, swine manure, wheat straw and corn straw were selected as raw materials for optimization of anaerobic co-digestion based on mixture design and central composite design. Three raw materials in mixture design were independent variables. The ratio of chicken manure and swine manure and the ratio of carbon and hydrogen in central composite design were independent variables. The methane potential was the response variable. The results indicated that the methane potential under co-digestion of three materials performed better than single and two components. The synergy effect of several materials improved the methane potential. Under optimized proportions, the actual methane potential was 1.62, 1.70, 1.66 and 1.73 higher than the expected value. Both mixture and central composite design were suitable for optimization the proportions of raw materials, but central composite design was more appropriate.