Colorectal cancer is malignancy that originates from epithelium lining of colon and rectum. GLOBOCAN reported that the incident in 2018 were 18 million new cases and 9.6 million deaths in global world. The Indonesian cases reached 34,189 in 2020. COX-2 suspected to play role in colorectal cancer carcinogenesis. Several studies have stated that any COX-2 expression in colorectal cancer, but research that shows correlation with prognostic factors is still controversial. This study aims to determine COX-2 expression in colorectal cancer using immunohistochemistry examination and the correlation with histopathological grading, depth of tumor invasion and regional lymph node metastasis. This research used analytical observational design, sample consisted of 30 paraffin blocks of colectomy patients diagnosed with colorectal cancer in 2022-2023 as well as medical record data from histopathological results. The analysis used univariate and bivariate analysis. Chi Square test results of COX-2 expression showed 100% positive staining with categories strong 93.4%, and moderate 6.7%. Results Spearman correlation test of COX-2 expression with histopathological grading obtained p value 0.856 (correlation not significant), correlation with the depth of tumor invasion obtained p value 0.763 (correlation not significant), and correlation with regional lymph node metastasis obtained p value of 0.023 (negative correlation). Overexpression of COX-2 was found in colorectal cancer and no correlation was found with the prognosis markers studied. Further research on COX-2 is needed by comparing other molecular markers such as KRAS, TP53, TILs.