Compared to animal miRNAs, plant miRNAs tend to have fewer targets that mainly encode transcription factors and F-box proteins. This indicts that miRNA is at the central position of gene expression regulatory networks of plant growth and development. Manipulation of mRNA transcript abundance via miRNA control provides a unique strategy for improvement of the complex agronomic traits of crops. In previous studies of our group, we have created 82 STTMs for targeting both conserved and species-specific miRNAs in Arabidopsis, and three STTMs in maize. Based on these STTM mutants, we have tried to explore the potential application of STTM technology in agronomic traits improvement. In Arabidopsis, we have generated a STTMmiR165/166 and STTMmiR160 double mutant by single mutant crossing. The double mutant plants exhibited a series of compromised phenotypes in leaf development and drought tolerance in comparison to phenotypic alterations in the single STTM lines. In maize, alternatively, we have screened according elite phenotypic variations in the three STTM mutants, almost without developmental defects. These elite mutant variations can be used for agronomic traits improvement via MAS. For example, STTMmiR166 mutants have superior drought tolerance, STTMmiR156 mutants have upward leaves, and STTMmiR172 mutants have excellent lodging resistance. Theses preliminary results offered useful theoretic and technical support for crop improvement by manipulating miRNA expression.