This study was done with the aim of investigating the mutual effect of butyric acid and genistein on performance, immune response and gut microbial populations in broiler chickens fed based on corn or wheat diets. For this purpose, a total of 480 Ross 308 broiler chicks were distributed in a completely randomized design with 8 treatments and 4 replications. Dietary treatments included; corn and wheat basal diet, additive-free diet (control), butyric acid, and both butyric acid and genistein, that were fed to the birds during a forty-two-day feeding trial. At the age of 9, 23, and 27 days, birds were vaccinated against Newcastle disease virus (NDV) and sera samples were collected after one week from vaccination. Moreover, chicks were vaccinated for Gumbro and infections bronchitis (IBV) viruses. On the days of 27 and 34, sheep red blood cells (SRBC) were injected and sera were collected one week after injection. At the age of 42 days, two birds from each cage were randomly selected, weighed, and slaughtered. After measuring internal organ weight, the ileal content was collected for ileal digestibility and microbial count. In general, the results of this study showed that the use of additives dietary improve body weight gain, and the amount of weight increase was more in the treatment of both butyric acid and genistein. The increase of butyric acid was more than that of the genistein’s. Feed intake was reduced with the use of additives dietary, whereas the decrease with the use of genistein was more than the decrease with butyric acid. The highest feed intake was related to chicks fed with wheat. The use of additives has caused significant feed conversion efficiency. The use of butyric acid lead to the lowest feed conversion ratio. The use of additives has increased abdominal fat. The use of additives and also mutual effects of dietary and additive were not significant. The use of additives in the diet may improve antibody titers against Newcastle on day 14 after vaccination, and the use of genistein improves the production of antibodies against sheep red blood cells. Use of butyric acid additive in the basal diet tended to increase triglyceride. In addition, use of genistein lead to a reduction in the amount of LDL. The use of additives has increased cholesterol levels. The use of additives reduced LDL concentration and the highest rate of reduction is related to the use of genistein. Base diet is effective on cholesterol levels. The lowest gut microbial population was observed in chickens based on corn diets. The total population of bacteria in the receiving groups of butyric acid was observed with the use of genistein. The results showed that the type of diets has not affected any subset of white globules in broilers. Additives reduced Heterophile and the greatest reduction was related to butyric acid. The use of additives lead to an increase of Lynfosit. It also lead to the decrease of eosinophils. Use of butyric acid resulted in the greatest reduction in the ratio of heterophil to lymphocyte. In general, it can be concluded that the mutual effect of butyric acid and genistein reduced the total bacterial population and also caused the largest increase in lymphocytes, which implies improvement of immune system. Keywords: Broiler chickens, Butyric acid, Genistein isoflavnoid, Performance, Immune response, gut microbial population