Background: Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore the therapeutic targets of CRC. Long non-coding RNA taurine upregulated gene 1 (LncRNA TUG1) was initially discovered as a transcript upregulated by taurine and is observed to be expressed in numerous human cancers. The Study Aim: This article was to explore the correlation between transforming growth factor-beta (TGF-β)/tumor protein 53 (P53) signaling mechanisms as regulators for LncRNA TUG1 in Egyptian patients with CRC. Subjects and Methods: Immunohistochemical (IHC) staining was achieved to study TGF-β and P53 expression in CRC specimens vs. normal colonic specimens and quantitative real-time PCR (qRT-PCR) was used to analyze LncRNA TUG1, TGF-β, and P53 relative gene expression in 96 tissue specimens (neoplastic specimens and the corresponding adjacent non-neoplastic specimens). Results: The expressions of LncRNA TUG1, TGF-β, and P53 were overexpressed significantly in CRC specimens as opposed to the matched neighboring non-neoplastic specimens (P<0.001), also LncRNA TUG1 was significantly positively correlated to the expression of TGF-β and P53 (r=0.89, 0.91 respectively, P<0.001). Conclusion: These findings reveal that LncRNA TUG1 may be a molecular component in the TGF-β/P53 signaling pathway, and LncRNA TUG1 could function as a CRC possible oncogene. LncRNA TUG1 may serve as a potential oncogene for CRC. The TGF-β/P53/LncRNA TUG1 interactions may be employed as potential targets for CRC diagnosis, prognostic evaluation, and cure.