The standard enthalpy of formation of 1115 compounds from all chemical groups, were predicted using genetic algorithm-based multivariate linear regression (GA-MLR). The obtained multivariate linear five descriptors model by GA-MLR has correlation coefficient (R-2 = 9830. 0). All molecular descriptors which have entered in this model are calculated from chemical structure of any molecule. As a result, application of this model for any compound is easy and accurate.