Abstract: The preparation conditions of alginate-chitosan-alginate (ACA) microcapsules with liquid core and good mechanical strengthwere optimized by response surface method. In the first optimization step，a Plackett-Burman design was used to evaluate the influence of related factors. The concentration and pH of chitosan solution have a positive effect to the membrane mechanical strength，while the pH of sodium citrate has a negativeeffect. The rest of other preparation conditions has no significant influence on the membrane mechanical strength. The path of steepest ascent was used to approach the optimal region of the optimized conditions subsequently. In the third step，the concentration and pH of chitosan solution and the pH of sodium citratethe were further optimized using central composite designs and response surface analysis. Verification experiment under the optimized conditions presented a Sw(%) value of －14.62%，which is in line with the theoretical value of －15.41%. Under the optimized condition，ACA microcapsules with liquid core demonstrate good performance in mass transferring and biocompatibility.