A novel ultrasensitive detection method utilizing surface-enhanced Raman scattering (SERS) based on monolithic column was developed in the present study. Monolithic column is a kind of chromatographic stationary phase that contains highly interconnected pores and absorbs chemical components efficiently. Dropping a mixture solution containing analyte, silver colloid, and NaCl on the surface in advance, SERS signals were collected on the surface of the monolithic column. With this method, five commonly used probe molecules of Rhodamine 6G (R6G), p-aminothiophenol, Rhodamine 123, crystal violet, thymine, and two chemicals that are used in agriculture (paraquat and flusilazole) were detected. Especially, R6G and p-aminothiophenol can be detected at extremely low concentrations of 10–18 and 10–16 mol/L at milliliter level, respectively. The enhancement factor was calculated to be approximately 1014 for R6G detection. The results suggest that the monolithic column does improve the sensitivity of SERS detection dramatically and the topography of the monolithic column is essential for the enhancement. The easy operability and the significant enhancement are the greatest advantages of this method. Copyright © 2012 John Wiley & Sons, Ltd.