Abstract: Due to the high spectrum dynamics of cognitive radio sensor networks, traditional routing protocols have drawbacks such as poor timeliness and high energy consumption. To address this issue, we propose a novel opportunistic forwarding-based routing (OFBR) protocol for cognitive radio sensor networks. The novelty of the OFBR protocol lies in its combination of short preamble sampling and opportunistic forwarding. In addition, we design a cognitive real-time forwarding condition that protects primary users and mitigates forwarding delay. The OFBR protocol can effectively reduce the overhearing and duty cycles of cognitive sensors by short preamble sampling, and thereby guarantees real-time and reliable transmission while protecting primary users by cognitive real-time forwarding. The OFBR protocol is a distributed routing protocol that requires only local information in the data routing process, so its routing overhead is significantly reduced. Extensive simulations confirm that the OFBR protocol obviously outperforms traditional routing protocols with respect to energy consumption and latency.