The proto-oncoprotein c-Myc and the tumour suppressor p53 interact in a negative feedback manner to maintain cellular homeostasis under physiological conditions: while c-Myc activates p53 through transcriptional regulation of ARF tumour suppressor (p14ARF in human and p19 ARF in mouse), p53 transcriptionally inactivates c-Myc and also represses c-Myc through microRNA-mediated mechanisms. However, the frequently imbalanced expression of c-Myc over p53 signifies that this interaction is paralysed in cancer cells. Although p53 suppression is frequently associated with the loss of ARF, we show here that c-Myc can alternatively inactivate p53 through a long noncoding RNA (lncRNA) that we name MILIP (c-Myc-inducible lncRNA inactivating p53). MILIP is commonly upregulated across diverse cancer types and is critical for cancer cell survival, division and tumorigenicity. When ectopically expressed, MILIP promotes c-Myc-driven transformation of normal epithelial cells. Mechanistically, MILIP restrains p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2) and thus facilitates p53 protein polyubiquitination and degradation. Collectively, these results uncover an inhibitory effect of c-Myc on p53 and demonstrate that MILIP functions as an accomplice that links c-Myc to suppression of p53. Therefore, MILIP may constitute a potential therapeutic target for cancer treatment.