To investigate the clinical efficacy and safety of the children with acute bacterial diarrhea when treated with Zhili Granule. Methods: A total of 120 children with acute bacterial diarrhea were collected from May 2013 to December 2015 in our hospital, all the patients were randomly divided into the control group and the observation group, and 60 cases in each group. Based on the illness state, all the patients of two groups were given oral probiotics, montmorillonite powder, vitamins and other supplements conventional treatment, the observation group was given Zhili Granule on the basis of conventional therapy, the treatment lasted for 3 days. Time duration of stopping diarrhea, stopping fever, signs and symptoms relieved and clinical efficacy, adverse events of two group were compared. Results: Time duration of stopping diarrhea, stopping fever, signs and symptoms relieved of the observation group were less than the control group, the differences were statistically significant (P<0.05). The markedly effective rate of the observation group was 70.00%, the total effective rate was 93.33%. The markedly effective rate of the control group was 31.67%, the total effective rate was 70.00%, the markedly effective rate and the total effective rate of the observation group were higher than the control group, the differences were statistically significant (P<0.05). No serious adverse events were recorded in two groups. Conclusion: The clinical efficacy and safety of Zhili Granule is clear when treating the children with acute bacterial diarrhea, it takes less time to stop diarrhea, fever and other symptoms with less adverse effect and better effect, which is worthy of clinical application.