The detection of antibiotics has attracted great attention among scientists and health researchers in the past decades. However, it is still difficult to realize the sensitive and selective detection of antibiotics with similar structures. Herein, the antibiotic molecules of oxytetracycline (OTC) can be sensitively and selectively detected by surface-enhanced Raman spectroscopy (SERS) on NH 2 −UiO-66(Zr)@Au nanoparticles (NPs). The SERS substrate of NH 2 −UiO-66(Zr)@Au NPs realizes a detection sensitivity of 1 × 10 −12 g•L −1 for 4-mercaptobenzoic acid, indicating its high SERS activity. A high detection sensitivity of 10 −11 g•L −1 is obtained for OTC on such a SERS substrate. Besides the high sensitivity, NH 2 −UiO-66(Zr)@Au NPs can also selectively detect OTC from streptomycin sulfate, salicylic acid, and ofloxacin by SERS on NH 2 −UiO-66(Zr)@Au NPs, with a selective detection limit of 10 −10 g•L −1 . Furthermore, OTC can be selectively detected in a real sample of river water with a detection limit of 1.0 × 10 −10 g•L −1 . Therefore, this study provides an effective way to enrich and detect antibiotics in real samples in the environment.