This paper aimed to optimize extracting conditions of SOD in Sedum aizoon by response surface method. First, the single factor optimization tests were carried out. Three single factors were time, pH and liquid-solid ratio respectively. By Design expert 8.0.5 software, 17 kinds of test scheme were designed. The protein yield of each scheme was obtained, and Design expert 8.0.5 software was used to conduct variance analysis and interactive analysis among factors, to obtain the corresponding mathematical model. The results showed that in single factor experiments, the optimal time was 1 h, pH was 7.8, and liquid-solid ratio was 15:1. The interactive analysis indicated that the optimal scheme for extracting SOD in Sedum aizoon was time of 0.98 h, pH of 7.79, liquid-solid ratio of 13.71:1. By the method of pyrogallol autoxidation, the extracted SOD enzyme activity was measured, namely 12 U/g. The results could provide a reference for further utilization and research of Sedum aizoon resource.