From the early demonstration of the E1B 55K–mutant dl1520 (a.k.a. ONYX-015), which selectively replicated in and killed p53-deficient human tumor cells (Bischoff et al., 1996), to the recent development of Ad5-3M virus that evades host innate immunity, rendering safe and efficient systemic cancer therapy (Atasheva et al., 2020), oncolytic adenoviruses (OAds) have consistently shown promising anti-cancer potentials. This evidence concerns the gene TP53 and cancer.