In integrated treatment of traditional Chinese medicine, prescriptions are used as carriers. Attention has been given to the integration, and the methodology of treatment is based on syndrome differentiation. To reveal the rule of drug group in prescription, according to the own drug efficacy of traditional Chinese medicine, Huo-Xue-Hua-Yu decoction (HXHYD) was divided into four drug-group decoctions as follow: Tiao-He drug group decoction (THDGD), Hua-Yu-Sheng-Xin drug group decoction (HYSXDGD), Huo-Xue-Zhi-Tong drug group decoction (HXZTDGD) and Bu-Qi drug group decoction (BQDGD). There are strong interactions between Ag nanoparticles and decoction, thus leading to a tremendous enhancement in the intensity of the decoction Raman scattering, the Surface-enhanced Raman Scattering (SERS) spectroscopy of HXHYD, THDGD, HYSXDGD, HXZTDGD and BQDGD were obtained and analyzed, and the characteristic Raman bands of five decoctions were tentatively assigned. Mainly eighteen Raman signals (523, 538, 622, 647, 732, 959, 977, 1 003, 1 048, 1 077, 1 145, 1 245, 1 326, 1 402, 1 456, 1 470, 1 518 and 1 605 cm-1) in five decoctions were discussed. Some Raman bands in SERS spectra of drug group decoctions were retained in the HXHYD, such as 538, 622, 647, 732, 959, 1 003, 1 048, 1 326, 1 402, 1 456, 1 470, 1 518 and 1 605 cm-1. However some Raman bands never appeared in the HXHYD, such as 1 077, 1 145 and 1 245 cm-1. New Raman bands were generated in the SERS spectra of HXHYD, such as 523 and 977 cm-1, which meant new created chemical compositions. The results showed that medical ingredients in the HXHYD were not the simple addition of THDGD, HYSXDGD, HXZTDGD and BQDGD, and SERS technique has great potential for providing a novel method for effectively and accurately studying drug group rule of prescription.