Interference in wireless sensor networks (WSNs) not only causes packet loss and delay, but also leads to excessive energy consumption. It is necessary to mitigate interference in order to improve transmission and energy efficiencies. To achieve this objective, a novel interference-aware routing (IAR) protocol based on crosslayer design was proposed. Unlike existing contention-based routing protocol, the IAR protocol employed interference degree and energy degree to make routing decision based on an interference-aware route selection scheme. Interference degree was computed based on received request-to-send (RTS), clear-to-send (CTS) and acknowledgment (ACK) packets, and energy degree of a node was calculated based on its initial and residual energy in order to prolong network lifetime. Simulation results show that the IAR protocol achieves higher energy efficiency and better performances than both dynamic codeword routing (DCR) and ad-hoc on-demand distance vector routing (AODV) protocols in terms of throughput, packet delivery ratio and delay.