Although there is a good amount of evidence that indicates that SFN is a potent anticancer compound and that its main mechanism of action would occur through the activation of Nrf2, recent publications present controversial results that indicate that the activation of Nrf2 contributes to the whole process of pathogenesis, promotes cancer progression and metastasis while conferring resistance to chemo- and radiotherapy, and has a poor prognosis, a phenomenon that has been described as the “dark side” of Nrf2 [28]. This evidence concerns the gene NFE2L2 and cancer.