Long non-coding RNAs (lncRNAs) associated with various cancers, including colorectal cancer (CRC), could be collected from body fluids easily. Our aims were to determine the expression level of HOTTIP lncRNA in plasma samples of healthy individuals and CRC patients as well as their relationship with clinico-pathological characteristics of patients. First, total RNA was extracted from the plasma samples of 100 subjects including 50 patients and 50 age and sex matched healthy persons. Then, gene expression was measured using real-time PCR technique. The sensitivity and specificity of HOTTIP dysregulation in CRC and healthy individual’s plasma was measured by receiver operating characteristic (ROC) analysis. As compared with healthy controls, HOTTIP lncRNA was over expressed in a statistically significant manner in plasma samples of patients (P = 0.001). Significant relationship between HOTTIP expression and positive family history of CRC was observed, too (P = 0.04). The ROC curve analysis showed an AUC value of 0.775, a specificity of 82%, a sensitivity of 76%, with a cut off value equal to 2.40 (P = 0.001). HOTTIP transcript can be proposed as a new biomarker for early diagnosis due to the increased expression in plasma samples of patients with CRC and the relatively high sensitivity and specificity.