Most of diseases are closely related to bactrerial infection while the fast and accurate detection of bacteria is always a focus subject which has attracted great attention by microbiologists and other relevant researchers. Raman spectroscopy can provide rich spectrum information, and surface- enhanced Raman Spectroscopy (SERS) has a high detection sensitivity, however, some of the noble metal SERS substrate will cause protein denaturation, which obtained the incorrect results. In this work, it is shown that Escherichia coli (E.Coli) can be detected by the SERS technique by using semiconductor nanoparticles as the substrate. The SERS spectrum of the E.Coli on the ZnO nanoparticle substrate with that on the Ag sol substrate was compared. The results indicated that stronger and richer SERS signals were observed on the Ag sol substrate compared with that on the ZnO substrate. However, an obvious difference was obtained between SERS spectrum of E.Coli on the Ag sol substrate and the Raman spectrum of bulk E.Coli, which could be due to the protein denaturation process. On the other hand, although the SERS signal of the E.Coli on the ZnO nanoparticles substrate is relatively weak, the signal is similar with that of the Raman spectrum of the bukl E.Coli, indicating that ZnO nanoparticles is an efficient and biocompatible SERS substrate for the detection of E.Coli. This study provides the important information for the non- destructive detection of bacteria by SERS technique based on the semiconductor nanoparticles substrate.