AbstractLeukemia inhibitory factor receptor (LIFR), in complex with glycoprotein 130 (gp130) as the receptor for leukemia inhibitory factor (LIF), can bind to a variety of cytokines and subsequently activate a variety of signaling pathways, including Janus kinase/signal transducer and activator of transcription 3. LIF, the most multifunctional cytokines of the interleukin‐6 family acts as both a growth factor and a growth inhibitor in different types of tumors. LIF/LIFR signaling regulates a broad array of tumor‐related processes including proliferation, apoptosis, migration, invasion. However, due to the activation of different signaling pathways, opposite regulatory effects are observed in certain tumor cells. Therefore, the role of LIFR in human cancers varies across different tumor and tissue, despite their recognized value in tumor treatment and prognosis observation is affirmed. Given its aberrant expression in numerous tumor cells and crucial regulatory function in tumorigenesis and progression, LIFR is considered as a promising targeted therapeutic agent. This review provides an overview of LIFR's initiating signaling pathway function as a cytokine receptor and summarize the current literature on the role of LIFR in cancer and its possible use in therapy.