Cadmium (Cd) is a strong toxic heavy metal pollutant, which poses a serious threat to plant development. Thus, it is vital important to understand the molecular mechanism of Cd accumulation, as to help reduce its potential toxicity to crops and maintain food security. MicroRNAs (miRNAs) act as critical gene regulators, participating in almost all abiotic stress processes. MiR535 is an ancient conserved miRNA, can be highly induced in the low concentration of Cd, but its biological functions in Cd stress is still unclear. In this study, we discovered that the OsSPL7 served as the main target gene of miR535. Moreover, rice overexpressing miR535 (OE535) promoted root length and Cd content, in contrast, plants knockout miR535 (mir535) and overexpressing OsSPL7 (SPL7myc) both had a reduced root length and Cd levels under Cd stress. Further, more Cd was translocated from rice husk to brown rice in OE535 plants but less translocated in mir535/SPL7OE plants. Most interesting and importantly, OsSPL7 could directly bind to the promoter of a major Cd transporter gene OsNramp5, and repress its transcripts levels to mediate Cd absorption. Collectively, this provides a new insight into the molecular basis of rice response to Cd stress by the miR535-SPL7-Nramp5 pathway.