Our results indicate that PB2 inhibits activation of NF‐κB/TLR4 and NLRP3 inflammasome, whereas simultaneous activation of Nrf2/Keap1 and AMPK/GSK3β signalling pathways may contribute to the antioxidant and anti‐inflammatory effects and thus alleviate CS‐induced liver injury. Here, NFE2L2 is linked to Cowden syndrome 1.