The biological functions of long non‑coding RNAs (lncRNAs) in cancer have not been fully elucidated. The present study demonstrated that the expression of a newly identified lncRNA, RP1‑85F18.6, was upregulated in colorectal cancer (CRC) tissues and cell lines. Knockdown of lncRNA RP1‑85F18.6 served a key role in tumor inhibition, reduced cell proliferation and invasion, disrupted the cell cycle, and increased apoptosis and pyroptosis of CRC cells. Conversely, overexpression of lncRNA RP1‑85F18.6 exerted the opposite effects. Furthermore, silencing lncRNA RP1‑85F18.6 decreased ΔNp63 expression at both the mRNA and protein levels. Furthermore, co‑transfection with ΔNp63 siRNA and lncRNA RP1‑85F18.6‑expressing vector attenuated the tumor‑promoting effects of lncRNA RP1‑85F18.6 overexpression. The expression levels of lncRNA RP1‑85F18.6, ΔNp63 and gasdermin D (GSDMD) were revealed to be associated with lymph node and distant metastases in patients with CRC, and therefore may serve as predictors in CRC. The findings of the present study suggested that lncRNA RP1‑85F18.6 may trigger CRC cell proliferation, invasion and cell cycle disruption, and suppress apoptosis and pyroptosis of CRC cells through regulating ΔNp63 expression. Therefore, lncRNA RP1‑85F18.6 and ΔNp63 may be considered unfavorable biomarkers, whereas GSDMD may be a favorable biomarker in CRC; these markers may prove valuable in the future diagnosis and prognosis of CRC.