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We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP) as an oncogenic driver. Our studies show that MILIP facilitates tumor protein p53 (TP53, best known as p53) turnover by reducing its SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2), thus promoting cell survival, proliferation, and tumorigenicity. MILIP may thus represent an anti-cancer target for counteracting the c-Myc axis.