The aim of this investigation was to determine the effect of using dried distiller grains with soluble (DDGS)  instead of cotton seed cake or soybean meal as a source of protein in ration formulation of growing crossed Friesian calves .Twenty - four crossed Friesian calves averaging 322 kg live body weight (LBW) were randomly chosen and divided into four groups ( 6 in each).Animals were received four experimental rations containing concentrate feed mixture (CFM), berseem hay (BH) and rice straw (RS) with rate of 60,25 and 15%,respectively.The CFM of ration B ,C and D contained cotton seed cake, soybean meal and dried distiller grains with soluble (DDGS), respectively as a source of 50% protein. CFM of ration A (control ration) contained the three previous items which gave 50% as a source of protein. The feeding trial lasted about 180 days, in which feed intake, body weight and feed utilization efficiency were determined. Four digestibility trials were carried out using acid insoluble ash (AIA) technique to determine digestibility coefficients and nutritive values of the experimental rations. The results showed significantly (P<0.05) increase in digestibility coefficient of all nutrients and feeding values of ration D (containing DDGS). Significantly increased in total and daily gains were observed in animals fed ration D, recording 202.21 and 1.125 kg, respectively. The feed efficiency expressed as kg DM/kg gain was significant (P<0.05) higher with ration D, while increasing in feed efficiency as kg TDN or DCP /kg gain was not significant. Moreover, ration D (containing DDGS) recorded the highest net revenue and economic efficiency with the lowest feed cost to get one kg weight gain. At the same time the rumen parameters and blood measurements with using DDGS in ration D showed no adverse effect and the parameters were within normal values. Generally, using DDGS as a source of protein in CFM in crossed Friesian calves rations increased digestibility , feeding values , daily gain, net revenue and decreased feed cost to get one kg gains. Moreover, rumen parameters and liver and kidney function measurements were normal with no adverse effect.