The heterogeneous network (HetNet), which deploys small cells such as picocells, femotcells, and relay nodes within macrocell, is regarded as a cost-efficient and energy-efficient approach to resolve increasing demand for data bandwidth and thus has received a lot of attention from research and industry. Since small cells share the same licensed spectrum with macrocells, concurrent transmission induces severe interference, which causes performance degradation, particularly when coordination among small cell base stations (BSs) is infeasible. Given the dense, massive, and unplanned deployment of small cells, mitigating interference in a distributed manner is a challenge and has been explored in recent papers. An efficient and innovative approach is to apply cognitive radio (CR) into HetNet, which enables small cells to sense and to adapt to their surrounding environments. Consequently, stations in each small cell are able to acquire additional information from surrounding environments and opportunistically operate in the spectrum hole, constrained by minimal inducing interference. This paper summarizes and highlights the CR-based interference mitigation approaches in orthogonal frequency division multiple access (OFDMA)-based HetNet networks. With special discussing the role of sensed information at small cells for the interference mitigation, this paper presents the potential cross-layer facilitation of the CR-enable HetNet.