In our current study, we demonstrate that fucoidan (i) promotes apoptosis of lung cancer cells, (ii) reduces lung tumorigenesis, (iii) induces ATF4 and CHOP protein expression in an LLC1-xenograft mice model via continuous oral feeding of fucoidan, and (iv) induces ROS-mediated ER stress via TLR4. This evidence concerns the gene TLR4 and lung cancer.