Covalent DNA-protein cross-links (DPCs), if not resolved, can block DNA replication and transcription, resulting in genome instability. Compared to other types of DNA damage, how DPCs are formed and repaired is less understood. This review focuses on recent findings concerning DPCs derived from two types of abasic DNA lesions, apurinic/apyrimidinic sites and 3'-phospho-α,β-unsaturated aldehydes. It summarizes the newly reported DPCs and their identification by liquid chromatography tandem mass spectrometry. It also reviews the approaches for synthesizing stable and site-specific DPCs, and their applications for discovering the corresponding repair mechanisms. Finally, it discusses the future directions to better understand the mechanistic formation and repair of those DPCs.