Background: Colorectal cancer (CRC) is a significant health issue albeit limited reports from Egypt. Long non-coding RNAs (lncRNAs) and circulating microRNAs (miRNAs/miRs) have been found to have dysregulated expression in CRC. Objective: This study aimed to investigate the use of miR-372 and lncRNA-HULC as noninvasive diagnostic biomarkers for CRC as well as to study the interaction between their expression levels in CRC. Methods: Using quantitative real-time PCR, the relative expression levels of miR-372 and lncRNA-HULC in serum were assessed in all study subjects (40 CRC patients and 30 healthy controls). Results: When compared to controls, serum expression levels of miR-372 and lncRNA-HULC were found to be significantly higher among CRC patients. According to receiver operating characteristic (ROC) analysis, which is the most popular approach of reporting the diagnostic accuracy of dysregulated ncRNAs, miR-372 had an AUC (an area under the curve) value of 0.76, sensitivity of 74.2%, and specificity of 96.4% at 7.8 cutoff point. Concerning lncRNA-HULC in the current study, AUC was 0.71 with sensitivity of 71.50% and specificity of 83.7% at 8.35 cutoff point. Conclusions: This study provided evidence that miR-372 and lncRNA-HULC are possible noninvasive diagnostic biomarkers for CRC. This work is the first that, as far as we know, to demonstrate the correlation between serum relative expression levels of miR-372 and lncRNA-HULC in CRC. Results of our study showed that high expression levels of miR-372 and lncRNA-HULC in serum could predict CRC and could distinguish CRC patients from healthy controls.