Most of the cultivated rice originated from ancestors that were semi-aquatic plants, having semi-prostrate stems bearing negligible seeds. It is not known how domesticated rice achieved delicate water relations during the transition to irrigated and gradually terrestrial ecosystem. Here, we show the involvement of an aquaporin that is differentially expressed between cultivated and wild rice, contributing to yield-related traits. Small (s)RNA-sequencing and degradome analysis identified specific targeting of this aquaporin by differentially expressing a well-conserved micro(mi)RNA named miR169. Although miR169 was previously implicated in stress tolerance, its targeting of aquaporin or the consequences of such a targeting were unknown. Using whole-genome approaches, such as sRNA-sequencing, RNA-seq, CRISPR-knockout lines, and stress assays, we show the involvement of this regulatory module in water-stress-associated traits. In agreement with its importance in domestication and yield-related traits, a known QTL for stress tolerance overlapped with this aquaporin. These results indicate yet another involvement of sRNA-mediated module in crop domestication.