In this study, eight potential functional strains were selected to interfered with RAW264.7 murine macrophages and human peripheral blood mononuclear cells (PBMCs). Then, changes in phagocytic activity of RAW264.7 cells and natural killer (NK) cell activity were detected and the screened potential probiotics were further intervened in BALB/c mice to explore their immunomodulatory efficacy in vivo. In cell experiments, the results showed that the intervention of different strains significantly increased the phagocytic activity of RAW264.7 cells (P0.05). In conclusion, Bifidobacterium bifidum FL-228.1 can improve innate immune function and have a more comprehensive effect on the immune system by regulating immune cell activity, cytokine expression and mRNA levels of immune molecules related to antimicrobial peptides.