Cancer is a complex pathology involving different genes and cellular pathways. A combination of treatments with different targets is thus required to eliminate cancer cells. This review deals with a new potential therapeutic approach: inhibiting a single RNA degradation pathway so as to inhibit tumorigenesis by acting on different cellular processes and on the expression of various genes. Also discussed is the re-expression of various genes: tumor suppressor genes harboring a nonsense mutation, NMD-silenced oncogenes, and genes inducing a specific anticancer immune response. Lastly, putative limitations of cancer treatment by NMD inhibition are addressed.