As p53 apoptotic function is often deregulated in tumors by different mechanisms, our results indicate that low HIPK2 expression is a potential marker for p53 dysfunction, tumor progressions, and chemoresistance; they also suggest some strategies, combining chemotherapy with pharmacological or natural agents, aimed at restoring p53 apoptotic transcriptional function in tumors with non-functional wtp53 and/or HIPK2. The gene discussed is TP53; the disease is neoplasm.