Cadmium (Cd) is a non-essential heavy metal with high toxicity to plants. MicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in plant abiotic stress responses. To investigate whether miRNAs function in Cd stress response, miRNA expression profiles in rice ( Oryza sativa ) under Cd stress were monitored using microarray assays. A total of 12 Cd-responsive novel miRNAs predicted previously were identified, of which 4 were further validated experimentally. A total of 44 target genes were predicted for the Cd-responsive miRNAs, many of which appeared to regulate gene networks mediating environmental stresses. Several target genes were validated to show a reciprocal regulation by miRNAs. A transgenic approach was also used to determine the role of miRNAs in rice response to Cd stress. Overexpression of miR192 retarded seed germination and seedling growth under Cd stress. These results implied the role of novel miRNAs in the involvement of Cd tolerance of rice.