Abstract: SET(Su(var), Enhancer of zeste (E(z)), and Trithorax) domain protein family members share the conserved SET domain. They participate in protein methylation, chromosome structure adjustment, and gene expression regulation, and play important roles in plant development. In this study, bioinformatics analysis identified 47 and 43 SET domain genes in Arabidopsis and rice, respectively. A comprehensive overview of this gene family was presented, including the gene struc-ture, phylogeny, chromosome distribution, and conserved motifs. As a result, the SET domain genes were organized into 5 subfamilies on basis of phylogenetic relationship. Chromosome localization and gene duplication analysis showed that segmental and retrotransposition-like event may result in the SET domain gene expansion. By analyzing the developmental expression pattern of SET domain genes in Arabidopsis and rice, most of the SET domain genes were shown to be expressed in at least one tissue with the most expression in flower and pollen. Some genes showed specific expression patterns in cer-tain tissues at certain stages, suggesting that they were closely related to tissue development. Differentially expressed genes were discovered in Arabidopsis and rice. All of the 4 differentially expressed genes in Arabidopsis were highly expressed in mature pollen. Three of the 4 differentially expressed genes in rice were highly expressed in stamen and the remaining one in young panicle.