Background: Node is the central organ of transferring nutrients and ions in plants. Cadmium (Cd) induced crop pollution threatens the food safety. Breeding of low Cd accumulation cultivar is a chance to resolve this universal problem. This study was performed to identify tissue specific genes involved in Cd accumulation in different rice stem nodes. Panicle node and the first node under panicle (node I) were sampled in two rice cultivars: Xiangwanxian No. 12 (low Cd accumulation cultivar) and Yuzhenxiang (high Cd accumulation cultivar). RNA-seq analysis was performed to identify differentially expressed genes (DEGs) and microRNAs. Results: Xiangwanxian No. 12 had lower Cd concentration in panicle node, node I and grain compared with Yuzhenxiang, and node I had the highest Cd concentration in the two cultivars. RNA seq analysis identified 4535 DEGs and 70 miRNAs between the two cultivars. Most genesrelated to the "transporter activity", such as OsIRT1, OsNramp5, OsVIT2, OsNRT1.5A, and OsABCC1, play roles in blocking the upward transport of Cd. Among the genes related to "response to stimulus", we identified OsHSP70 and OsHSFA2d/B2c in Xiangwanxian No. 12, but not in Yuzhenxiang, were all down-regulated by Cd stimulus. The up-regulation of miRNAs (osa-miR528 and osa-miR408) in Xiangwanxian No. 12 played a potent role in lowering Cd accumulation via down regulating the expression of candidate genes, such as bZIP, ERF, MYB, SnRK1 and HSPs. Conclusions: Both panicle node and node I of Xiangwanxian No. 12 played a key role in blocking the upward transportation of Cd, while node I played a critical role in Yuzhenxiang. Distinct expression patterns of various transporter genes such as OsNRT1.5A, OsNramp5, OsIRT1, OsVIT2 and OsABCC1 resulted in differential Cd accumulation in different nodes. Likewise, distinct expression patterns of these transporter genes are likely responsible for the low Cd accumulation in Xiangwanxian No. 12 cultivar. MiRNAs drove multiple transcription factors, such as OsbZIPs, OsERFs, OsMYBs, to play a role in Cd stress response.