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As a common lethal disease, cancer is now responsible for the majority of deaths worldwide and has been the single most important barrier to increasing life expectancy in the world. The pathogenesis of cancer has been the key point of cancer therapeutics research. The primary cilium, a solitary microtubule-based organelle, is considered to be an important sensor for receiving mechanical and chemical stimulation from other cells and environments; it plays an important role in a variety of signal transduction and disease processes. More importantly, the primary cilium can also function as an elaborate structure to regulate cell proliferation because ciliogenesis regulates cell division by sequestering the centriole. Recently, many new findings have suggested that the length and incidence of the primary cilium are closely connected to carcinogenesis and responses to cancer therapy. Here, we review relevant evidences proving that the primary cilium plays a key role in the occurrence and treatment of cancer. We also summarize the primary cilium-associated signaling pathways in cancer, including Wnt signaling, Hedgehog signaling, PDGFR signaling, and Notch signaling, and anticipate that targeting proteins localized in the primary cilium may be a potential anti-cancer strategy. [ABSTRACT FROM AUTHOR]