Pre-harvest sprouting (PHS) results in lower yields for rice and other crops, especially in rainy season before harvest. By using gene based functional studies to reveal the mechanism of PHS related pathways can be a good way in breeding for more PHS resistant accessions. Orthologous genes, which are homologous genes that diverged after a speciation event, generally maintain a similar function in different species to that of the ancestral gene in which they evolved from. Applied with a McDonald-Kreitman Test (MKT), we examined more than 10,000 orthologous genes between rice (Oryza sativa) and Brachypodium (outgroup) based on different phenotypic groups in order to find some fast evolutionary genes in rice PHS. Three groups which represented the PHS susceptible (group 1), PHS medium (group 2) and PHS resistant (group 3) were separated based on the phenotype and each group was examined with the outgroup for MKT. Total 60 fast evolutionary genes that have a positive selection with FDR ≤ 0.05 were found in the three groups, and 19, 5 and 8 genes were specific existed in group 1, 2 and 3, respectively. Annotation of these genes were conducted and the predicted functions were investigated, leading that one Ethylene receptor-like gene that may related to PHS based on the previous studies, which need to be validated later, however. In addition, network analysis of these characterized genes were also investigated, which could reveal the connection of genes between each other. Moreover, the association study between the candidate gene ethylene receptor and the PHS phenotype was performed and indicated that this gene is significantly correlated with PHS in rice. All these above indicated that with this orthologous based method, we can find some important candidate genes that may play an important role in some traits.