Normal Raman spectroscopy and surface-enhanced Raman spectroscopy of aspirin and aspirin tablet were reported, and the vibrational and enhanced peaks were assigned; the interaction of aspirin with DNA was investigated by SERS and UV. The results showed that NRS and SERS of aspirin and aspirin tablet were consistent basically, which indicated that excipient hardly affected the detection of aspirin; in SERS, aspirin was absorbed perpendicularly on silver colloid through the carboxyl group and the benzene ring; The interaction was mainly caused by the inserting-action mode between aspirin and DNA, and the benzene ring and CO of aspirin were inserted between the base pair of the double helix structure of DNA, which provided important information and useful reference for understanding deeply the mechanism of action of this kind of drug.