Colorectal cancer (CRC) represents a major burden for public healthcare as the third most common malignancy globally and the second leading cause of cancer deaths .More than one-third of colorectal cancer cases in Egypt include people under the age of 40 who are found to have the disease at an advanced stage. Due to its function in human tumours, cyclooxygenase (COX), a crucial enzyme in the prostanoid biosynthesis pathway, has drawn a lot of interest. COX-2 regulates cell proliferation, cell transformation, tumour growth, metastasis, and invasion, and so plays an important role in the origin and development of metaplastic and dysplastic tissues, as well as the beginning and progression of cancer. Increased COX-2 expression has been linked to a variety of epithelial-based premalignant and malignant lesions in the gastrointestinal system, including the colorectal area .A review of the available databases and literature and our own data have identified some interesting molecules induced by prostaglandins or COX-2 that have been also described to play a role in colon cancer, being thus potential pharmacological targets in colon cancer. Among those DUSP4, and 10, ,Trop2, and many from the TGFβ and p53 pathways have been identified as genes upregulated in response to COX-2 overexpression or PGs in colon carcinoma lines and overexpressed in colon tumor tissue. In this review we will give an overview about possible role of Cyclooxygenase-2 in Colorectal Cancer Progression. In conclusion, Considerable amounts of evidence in clinical settings further support a role of COX-2 in colorectal carcinogenesis and tumor progression. Thus, COX-2 is expressed early during the adenoma- carcinoma sequence that occurs in CRC, suggesting an important role of this enzyme in colorectal carcinogenesis. COX-2 expression is upregulated in human colorectal adenocarcinomas when compared with normal adjacent colonic tissue