In order to continue and to study in detail how xanthohumol, phenethyl isothiocyanate, resveratrol, indole-3-carbinol, and their combinations modulate the Nrf2 pathway, and how this modulation can correspond with the NF-κB signaling pathway, we focused on the evaluation of the effect of these phytochemicals on Nrf2 canonical and non-canonical pathway activation, as well as the interaction between Nrf2 and NF-κB, and STATs signaling pathways in extensively proliferating pancreatic cancer cell line—PSN-1 and tumor growth in vivo. Here, NFKB1 is linked to familial pancreatic carcinoma.