Colorectal cancer (CRC) remains among the topmost malignancy across the globe. It stands to be the leading cause of cancer mortality worldwide. It is the second most common cancer diagnosed in women and the third most in men that accounts for approximately 10% of cancers diagnosed annually. It will be worthwhile to identify and measure the dysregulated protein marker in order to comprehend illness pathobiology and improve disease diagnosis and therapy. This study utilizes high throughput quantitative tissue proteomics approach to study the dysregulation. This work aimed at examining proteomic dysregulation in human CRC tissue samples as compared to matched peritumoral tissue from a diverse patient population of Indian origin using Tandem Mass Tag (TMT) to identify potential biomarkers. The altered proteins from the study were further taken for biological pathway analysis to decipher the insights of disease biology. This study is one of the first comprehensive proteome-wide investigations of Indian CRC patients detecting potentially altered protein candidates in the disease development and metastasis which can be used as a potent biomarker.