Abstract Background Iron (Fe) is an essential element for plant growth and development, whereas cadmium (Cd) is non-essential and highly toxic. Previous studies showed that Fe deficiency enhanced Cd uptake and accumulation in peanuts. However, the molecular mechanism underlying the increased Cd accumulation in Fe-deficient peanut plants is poorly understood. Results We employed a comparative transcriptome analysis approach to identify differentially expressed genes (DEGs) in peanut roots exposed to Fe-sufficient without Cd, Fe-deficient without Cd, Fe-sufficient with Cd and Fe-deficient with Cd. Compared with the control, Fe deficiency induced 465 up-regulated and 211 down-regulated DEGs, whereas the up- and down-regulated DEGs in Cd exposed plants were 329 and 189, respectively. Under Fe-deficient conditions, Cd exposure resulted in 907 up-regulated DEGs and 953 down-regulated DEGs. In the presence of Cd, Fe deficiency induced 1042 up-regulated and 847 down-regulated genes, respectively. Based on our array data, we found that metal transporter genes such as CAX4, COPT1, IRT1, NRAMP5, OPT3, YSL3, VIT3 and VIT4 might be involved in iron homeostasis. Moreover, combined with quantitative real-time PCR, IRT1, NRAMP3, NRAMP5, OPT3, YSL3, ABCC3, ZIP1, and ZIP5 were verified to be responsible for Cd uptake and translocation in peanut plants under iron deficiency. Additionally, a larger amount of ABC transporter genes was induced or suppressed by iron deficiency under Cd exposure, indicating that this family may play important roles in Fe/Cd uptake and transport. Conclusions The up-regulated expression of NRAMP5 and IRT1 genes induced by iron deficiency may enhance Cd uptake in peanut roots. The decrease of Cd translocation from roots to shoots may be resulted from the down-regulation of ZIP1, ZIP5 and YSL3 under iron deficiency.