Molecular changes have a substantial impact on the onset of colorectal cancer (CRC). Complexes of HOTAIR and miRNAs disrupt several cellular functions during carcinogenesis, primarily by disrupting several carcinogenic signaling pathways. In the present study, the relationships between the serum levels of transforming growth factor-β1 (TGF-β1), sirtuin-1 (SIRT1) and E-cadherin and those of HOX transcript antisense intergenic RNA (HOTAIR) and microRNA-130a (miR-130a) in individuals with CRC were analyzed, including their correlations and diagnostic potential. Patients with colon cancer and healthy volunteers were enrolled in the study. Blood samples were collected from 70 patients with CRC and 30 age-matched healthy control volunteers and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the serum levels of HOTAIR and miR-130a. In addition, the levels of TGF-β1, SIRT1 and E-cadherin were determined utilizing enzyme-linked immunosorbent assays. Patients with CRC were found to have significantly higher TGF-β1, SIRT1, HOTAIR and miR-130a serum levels than those of healthy participants. In addition, patients with high-grade CRC had significantly higher levels of TGF-β1, SIRT1, HOTAIR and miR-130a compared with those of patients with low-grade CRC. A significant reduction in the serum levels of E-cadherin was observed in participants with CRC compared with healthy participants, but no significant difference was detected according to the grade of CRC. Positive correlations were found between HOTAIR and miR-130a, as well as TGF-β1 and SIRT1. By contrast, negative correlations were noted between E-cadherin and HOTAIR, miR-130a, TGF-β1 and SIRT1. Therefore, it may be concluded that the miR-130a/HOTAIR and TGF-β1/SIRT1/E-cadherin axes may serve as novel biomarkers for the early diagnosis of CRC.