The cyclopentenone prostaglandin A2 (PGA2) exhibits potent antiproliferative and antitumor activities both in vitro and in vivo, leading to cell cycle arrest associated with a dramatic decrease in the levels of cyclins and cyclin-dependent kinases(CDKs), and accompanied by an obvious increase of the expression of one of the cdk inhibitors, p21waf1/cip1. p21 waf1/cip1 protein(p21) can also mediate p53 dependent or p53-independent G1 arrest of many cell types, and plays an important role in PGA2-induced cell cycle arrest. Latest progress on the role of interaction of p21 and transcription factor E2F played in PGA2-mediated cell cycle arrest is reviewed.