Abstract: Objective To investigate the effects of different probiotics on intestinal flora, serum tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in neonatal antibiotic-associated diarrhea. Methods A total of 78 children with antibiotic-related diarrhea were randomly divided into observation group and control group, with 39 cases in each group. The control group took Saccharomyces boulardii, and the observation group took Combined Clostridium Butyricum and Bifidobacterium Powders. The diarrhea situation and clinical efficacy were compared between the two groups, and the changes of number of intestinal flora as well as serum TNF-α and IL-6 level before and after treatment were compared. Results There was no significant difference between the two groups in the time from antibiotics to diarrhea(P>0.05). The duration of stopping diarrhea and hospitalization time in the observation group were significantly shorter than those in the control group(P<0.05). After 3 days of treatment, the number of bifidobacteria, eubacteriums and lactobacillus in feces of the two groups was significantly higher than those before treatment, while the number of bifidobacteria, eubacteriums and lactobacillus in the observation group was significantly higher than those in the control group(P<0.05); the serum TNF-α and IL-6 levels were significantly lower in the observation group than those in the control group(P<0.05). The total clinical effective rate of the observation group was 89.74%, which was significantly higher than 69.23% of the control group(P<0.05). Conclusion The treatment of antibiotic-associated diarrhea and Combined Clostridium Butyricum and Bifidobacterium Powders can effectively shorten the diarrhea and hospital stay in children, significantly increase the number - of intestinal flora and reduce inflammatory response.