An experiment was conducted to replace soya bean meal (SBM) with cashew nut meal (CNM) in the diet of tilapia (Oreochromis mossambicus). Five isonitrogenous (30% CP) and isolipidic (6% CL) diets, CNM0 to CNM4, were prepared replacing SBM at 0%, 12.5%, 25%, 37.5% and 50% with CNM. The feeding trial was conducted in FRP digestibility tanks of 150 L capacity for 60 days. Twenty tilapia fry (20.56 ± 0.05 g) were stocked in each tank. The final weight, weight gain and weight gain% of tilapia that received the CNM4 diet were significantly higher (p < .01) among the treatments. The significantly higher nutrient utilization efficiency in terms of FCR, PER, PRE and LRE was obtained in the CNM4 group. Similarly, a significantly lower (p < .01) body moisture content and a significantly higher (p < .05) body protein content were also observed in the CNM4 diet‐fed group. In tilapia fed the CNM4 diet, the activity of both protease and amylase enzymes was significantly higher (p < .05), but the amylase:protease ratio (A:P) was significantly lower (p < .05). Protease, amylase and A:P were positively correlated with the nutrient digestibility coefficient. The serum protein, albumin and globulin of tilapia fed the CNM4 diet were significantly higher (p < .05) and the liver status enzymes did not vary (p > .05) among the treatments. It can be concluded from the study that 50% replacement of SBM with CNM in the diet is suitable for the enhancement of growth, nutrient utilization and health status of tilapia.