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The oxidative stress-sensing transcription factor Nrf2 has been studied by cancer researchers as a double-edged sword that can either promote or inhibit cancer. Previous findings have shown that Nrf2 can act as a tumor suppressor by detoxifying carcinogens. Paradoxically, when cancer cells express Nrf2, they are protected from oxidative stress and certain chemotherapies, thus explaining why some cancer cells constitutively activate Nrf2 as a tumor promoter. We recently found that the cytokine Interleukin (IL)-17D mediates the recruitment of natural killer (NK) cells to tumor sites, thereby leading to tumor rejection. Here, we show that Nrf2 induced IL-17D in primary tumors and tumor cell lines. Moreover, the known Nrf2-activator tBHQ induced Nrf2 and IL-17D simultaneously, without creating harmful oxidative stress. Applying a tBHQ-containing skin cream to established tumors led to NK cell-mediated tumor regression, and this depended on IL-17D and Nrf2. We propose that the use of tBHQ or other Nrf2 activators can intiate a tumor surveillance pathway involving IL-17D and NK cells, thus mediating cancer regression and bearing potential for cancer immune therapy.