We have recently applied the technique of drop coating deposition Raman (DCDR) spectroscopy for colorectal cancer (CRC) detection using blood plasma. The aim of this study was to develop a more convenient and stable method based on blood plasma for noninvasive CRC detection. Significant differences are observed in DCDR spectra between healthy () and cancer () plasma from 15 CRC patients and 21 volunteers, particularly in the spectra that are related to proteins, nucleic acids, and -carotene. The multivariate analysis principal components analysis and the linear discriminate analysis, together with leave-one-out, cross validation were used on DCDR spectra and yielded a sensitivity of 100% () and specificity of 98.1% () for detection of CRC. This study demonstrates that DCDR spectroscopy of blood plasma associated with multivariate statistical algorithms has the potential for the noninvasive detection of CRC.