ABSTRACT: Arsenic (As) contamination in subsoil and groundwater is a big problem, especially in many South-East Asian countries. As a staple crop growing under flooded condition in these areas, rice (Oryza sativa L.) becomes a big threat to human health through the food chain since As is highly accumulated in grains. Thus, reducing As accumulation in rice through molecular breeding and identification of rice varieties with low As content are the pressing issues. However, the current understanding on the molecular mechanism of As stress response is still limited for rice. In this study, we performed a comprehensive search for the As-responsive small RNAs (sRNAs) of rice. Briefly, 4,762 and 18,152 sRNAs were identified to be highly activated under As stress in roots and shoots respectively, while 14,603 and 8,308 sRNAs were intensively repressed by As treatment in roots and shoots, respectively. A number of the As-responsive sRNAs found their loci on tRNAs, rRNAs or long non-coding RNAs (lncRNAs). Interestingly, these loci preferentially distributed on the 5' halves of the tRNA, rRNA or lncRNA precursors. Among the above-identified As-responsive sRNAs, 252 Argonaute 1 (AGO1)-enriched sRNAs were extracted for target identification, resulting in 200 pairs of sRNA-protein-coding target interactions. Many targets are functionally involved in the development, stress response, reproduction, or lipid metabolism. Additionally, 56 lncRNAs were discovered to be targeted by nine AGO1-enriched sRNAs, indicating the potential involvement of these lncRNAs in As signaling. Taken together, our results could expand the understanding on the non-coding RNA-mediated As stress response in rice.