p62 is a stress‐inducible protein able to change among binding partners, cellular localizations and form liquid droplet structures in a context‐dependent manner. This protein is mainly defined as a cargo receptor for selective autophagy, a process that allows the degradation of detrimental and unnecessary components through the lysosome. Besides this role, its ability to interact with multiple binding partners allows p62 to act as a main regulator of the activation of the Nrf2, mTORC1, and NF‐κB signaling pathways, linking p62 to the oxidative defense system, nutrient sensing, and inflammation, respectively. In the present review, we will present the molecular mechanisms behind the control p62 exerts over these pathways, their interconnection and how their deregulation contributes to cancer progression. p62/SQSTM1 interacts with key regulator proteins for diverse signal transduction pathways including mTORC1 activation, NF‐κB signaling, the Keap1‐Nrf2 system, and selective autophagy and serves as a signaling hub for anabolism, inflammatory response, antioxidant response, and catabolism. In this State‐of‐the‐Art Review, we discuss about diverse roles of p62/SQSTM1 and about their deregulation in cancer.