The effects of different prebiotics and oxygen scavengers on making the process of xanthan gum and chitosan (XC) Bifidobacterium bifidum BB01 microcapsules were studied by single factor experiment and Plackett-Burman screening test, ascorbic acid, sodium erythorbate and xylo-oligosaccharide had significant effects. Based on the previous studies, the process XC B. Bifidum BB01 microcapsules were further optimized by Box-Behnken model in this study. Response surface analysis showed that the best additive amoumt of ascorbic acid, sodium erythorbate and xylo-oligosaccharide were 3.0%, 2.36% and 4.99%, respectively. The viable counts of B. Bifidum BB01 microcapsules reached to 1.52×1010CFU/g from 1.25×1010 CFU/g, the encapsulation yield reached to 94.88% from 90% under the optimum conditions. It provided the research foundation for the afterward production and exploration of the process XC B. Bifidum BB01 microcapsules.