Metal–organic framework (MOF) compounds are centered on metal ions or metal ion clusters, forming lattices with a highly ordered periodic porous network structure by connecting organic ligands. As MOFs have the advantages of high porosity, large specific surface area, controllable pore size, etc., they are widely used in gas storage, catalysis, adsorption, separation and other fields. SERS substrate based on MOFs can not only improve the sensitivity of SERS analysis but also solve the problem of easy aggregation of substrate nanoparticles. By combining MOFs with SERS, SERS performance is further improved, and tremendous research progress has been made in recent years. In this review, three methods of preparing MOF-based SERS substrates are introduced, and the latest applications of MOF-based SERS substrates in biosensors, the environment, gases and medical treatments are discussed. Finally, the current status and prospects of MOF-based SERS analysis are summarized.