Excess enthalpy is an important basic data of modern scientific research and engineering design, and it is difficult to predict accurately. The authors have pointed out that the properties of the solution depend on the organic connections and mutual constraints of all the molecules that make up the solution, and this synergy is not a simple superposition of individual interactions between the same molecules or heterogeneous molecules, but shows a complex synergistic behavior of the whole. Compared with pure liquid, the composition and properties of solution are special because molecular interaction forms special aggregates and in the special synergy of intermolecular forces. According to this, the three-factor model of excess enthalpy is constituted. On this basis, the key parameters of the model were quantitatively characterized by Wiener index, and a two-parameter model of excess enthalpy of a series of solutions composed of pentanone-2 and C3~C8 fatty alcohols was established, which was tested with experimental data. The results show that the calculated value of the new model is close to the calculated value of the three-parameter model proposed by the author, and slightly better than the calculated value of the three-parameter model proposed by Liu Guojie.