<p>Mitogen-activated protein kinases are the most crucial pathways involved in cellular homeostasis. Aberrations in this signalling cascade have been implicated in the pathogenesis of neoplasia. They prove to be a key modulator in tumorigenesis as they extend their influence in all aspects of tumorigenesis. They further enhance cancer progression by accelerating neoplastic cell proliferation, differentiation, apoptosis inhibition, metastasis &amp; invasion. In a nutshell, this pathway proves to be a prime hub for molecular targeting in combating cancer. Polyphenols are a class of compounds which play a potent role in impeding neoplastic progression. They are known to modulate each step of tumorigenesis thus hindering cancer metastasis as well as invasion. Research suggests that polyphenols exhibit promising results for the treatment of cancer by modulating the mitogen signalling pathway. Dietary polyphenols deserve a special emphasis for combating tumorigenesis with greater therapeutic efficacy. The fundamental objective of this manuscript is to meticulously analyse the role of mitogen-activated protein kinases in neoplasia &amp; recognise possible sites for molecular targeting. It also extensively discusses how polyphenols hinder cancer progression and how this property can be exploited for the benefits of patients. The effect of polyphenols on the majority of cancers have been intricately discussed. The challenges &amp; future prospects are also enumerated for clearly defining the research question for the future decades.</p> Graphical Abstract <p></p>