Background: One of the most prevalent gastrointestinal diseases is colorectal cancer (CRC). In CRC tissues and plasma, the long noncoding RNA (lncRNA) ITGB8-AS1 is abundantly expressed and can promote migration, colony formation, and proliferation of cancer cells. Objective: This study aimed to evaluate the clinical correlations of lncRNA ITGB8-AS1 and its potential as a diagnostic marker for colorectal cancer. Patients and methods: Twenty patients with benign colorectal lesions, twenty patients with colorectal cancer, and twenty healthy volunteers were enrolled in total. The lncRNA ITGB8-AS1 was assessed using a quantitative real-time polymerase chain reaction. Results: Compared to patients with benign lesions or the control group, patients with colorectal cancer showed higher levels of carcinoembryonic antigen (CEA), CA19-9, and lncRNA ITGB8-AS1. The combined use of lncRNA ITGB8-AS1, CA19-9, and CEA achieved high accuracy (97.5%), with 100% specificity and 95% sensitivity. Logistic regression identified lncRNA ITGB8-AS1 as a significant independent predictor with an adjusted odds ratio of 32, outperforming other markers. Furthermore, lncRNA ITGB8-AS1 showed significant correlations with parameters such as platelet count, PT, INR, CEA, and CA19-9, and a negative association with hemoglobin. Its levels increased with higher tumor stages and grades Conclusions: This study supported the promise of lncRNA ITGB8-AS1 as a novel biomarker by highlighting its strong diagnostic potential in colorectal cancer. It does this by showing that it is significantly upregulated, performed exceptionally well as an independent predictor, and had meaningful correlations with tumor markers and laboratory parameters, particularly when combined with CEA and CA19-9.