<p>p21 ^{(Cip1/Waf1/Sdi1)}, a widely studied member of the CKI (CDK inhibitor) family, has been designated a negative regulator of cell cycle progression. As a transcriptional target of p53, p21 arrests the cell cycle by suppressing the activity of cyclin-CDK complexes upon DNA damage in a p53-dependent manner to prevent oncogenesis; however, p21 exhibits dichotomous behavior in oncogenic signaling. It can either prevent or promote tumorigenesis. Such a controversial action of p21 is believed to depend on the intracellular localization of the protein. The anti-cancerogenic activities of p21 are related to its nuclear localization, whereas its cytoplasmic localization is associated with its pro-cancerogenic effects. Post-translational modifications (mainly phosphorylations) of p21 determine its intracellular localization, which is responsible for the ultimate cell fate, i.e., death or life. In this review, we have briefly summarized the dual face of p21 in oncogenesis (pro- and anti-) and elaborated on its compartment-specific functions and how this binary aspect of p21 in cancer is regulated by its post-synthesis modifications, which will enhance our perception of its characterization in carcinogenesis.</p> Graphical Abstract <p></p>