Background <p>Colorectal cancer (CRC) is the third most frequent cancer and the second deadliest cancer, worldwide. Long noncoding RNAs (lncRNAs) have been introduced as crucial regulators of CRC. lncRNA feline leukemia virus subgroup C receptor 1 antisense RNA 1 (<i>FLVCR1‑AS1</i>) is suggested to play a significant role in the tumorigenesis of several cancers. The Wnt signaling pathway is the most deregulated pathway in CRC.</p> Objective <p>The present study aimed to investigate the underlying mechanism of function of <i>FLVCR1</i>-<i>AS1</i> in CRC through <i>FLVCR1-AS1</i>/miR-381-3p/<i>CTNNB1</i>, <i>LRP6</i>, and <i>FZD3</i> axis.</p> Methods <p>The expression levels of FLVCR1-AS1 were analyzed in colorectal cancer (CRC) tissues compared to adjacent normal tissues, as well as across various CRC cell lines. In HCT116 cells, FLVCR1-AS1 was knocked down, and the subsequent effects on the expression levels of FLVCR1-AS1, miR-381-3p, and three genes were measured using real-time PCR. Proliferation differences were assessed through an MTT assay, while cell death was evaluated using flow cytometry.</p> Results <p>The results confirmed that <i>FLVCR1</i>-<i>AS1</i> was upregulated in CRC tissues compared to adjacent normal tissues. RT-qPCR validated that <i>FLVCR1-AS1</i> has the most level of expression in HT29, HCT116, SW480, and Caco2; respectively. Knockdown of <i>FLVCR1</i>‑<i>AS1</i> was significantly followed by attenuated viability of HCT116 cells; while resulted in enhancement of apoptosis and necrosis.</p> Conclusion <p>These findings support the idea that <i>FLVCR1</i>-<i>AS1</i> may act as an oncogene in CRC, and targeting <i>FLVCR1-AS1</i>/miR-381-3p/<i>CTNNB1</i>, <i>LRP6</i>, and <i>FZD3</i> axis may be introduced as a novel target for CRC therapy and diagnosis in the future.</p>