In-situ microcalorimetry was used to obtain the molar surface Gibbs energy, molar surface enthalpy and molar surface entropy of Cu2O nanoparticles, and their influences of particle size and morphology were investigated. The activity and mechanism of photocatalytic degradation of methyl orange were discussed with a correlation between the Cu2O surface energy.Results indicated that the surface thermodynamic functions increased with the decrease of the particle size. The Cu2O surface energy was of the following order: spherical>octahedral>tremella-like with corresponding values of 9.826, 8.438 and 6.901kJmol−1, respectively. The order of catalytic activity was tremella-like>particle spherical>octahedral with a corresponding degradation rate of 94.79, 70.10 and 68.19%, respectively. The photocatalytic activity was significantly related to surface energy. Interestingly, we found that nano-Cu2O with low surface energy exhibited a high photocatalytic activity. This study provided a new understanding of the surface-activity relationship between nanomaterial surface energy and catalytic properties.