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Endogenous Retroviruses (ERVs) are originated from ancient exogenous viruses, which integrate into the host genome after infection and persist across all vertebrate lineages. Complete ERV consists of viral genes (gag, pro, pol, and env) in the center and two Long Terminal Repeats (LTRs) at both ends, which encode viral structural proteins, critical enzyme, and glycoprotein. ERVs constitute approximately 8% of human genome and function in a wide range of physiological and pathological processes, including embryonic development, inflammation and infection, neurodegenerative diseases, cancers, etc. The expression of ERVs is controlled mainly by epigenetic modification, transcriptional regulation and post-transcriptional modulation, which offered important therapeutic targets. In this review, we reviewed the structure and function of ERVs, summarized recent research advances on how ERVs contribute to cancer initiation and progression, and introduced some therapies targeting ERVs.