PNAS-4 is a novel pro-apoptosis gene identified latetly. In recent years, there has been a large number of research reports on the basic studies about PNAS-4 in cancer gene therapy and gene therapy of PNAS-4 alone or combined with chemotherapy or radiotherapy manifested a good application prospect, but its molecular mechanisms to promote apoptosis is not clear yet. In this paper, recent research about PNAS-4 in cancer gene therapy is briefly reviewed, and recent hypotheses on its molecular mechanisms to promote apoptosis are especially elucidated. Based on its newly identified characteristics of structural domain, we made a point that PNAS-4 might regulate functions of some target protein related to apoptosis by deSumoylation as a new deSumoylating isopeptidase, and consequently promote apoptosis.