Sodium dodecyl sulfate (SDS) is widely used in sample preparation for proteomic research. However, SDS is incompatible with liquid chromatography and electrospray ionization (ESI). SDS depletion is therefore required ahead of liquid chromatography coupled with mass spectrometry (LC-MS) analysis. Most of current SDS removal strategies are time-consuming, laborious and low reproducibility. Here, we describe a method, SDS-cyclodextrin assisted sample preparation (SCASP), by which cyclodextrin can bind to SDS and form cyclodextrins-SDS complexes in solutions, allowing for direct tryptic digestion. We demonstrate that SCASP is a simple, fast and robust SDS-based sample preparation method for proteomics application.