Microcystin-LR (MCLR) and linear alkylbenzene sulfonate (LAS) are present widely in aquatic and terrestrial ecosystems, but their combined ecotoxicological risk is unknown. This study investigated the toxic effects of MCLR, LAS and their mixture on lettuce (Lactuca sativa L.) and evaluated MCLR accumulation level in lettuce with or without LAS. The changes in seed germination and shoot/root growth, responses of the antioxidative defense system, and the accumulation of MCLR in lettuce were tested to evaluate the single and combined toxic effect of MCLR and LAS in well-controlled conditions. The results showed that seedling growth (except for root elongation and leaf weight) was more sensitive to toxicant exposure than seed germination. For seedling leaves, lipid peroxidation was not observed when the antioxidative defense system (including superoxide dismutase, catalase and glutathione) was activated to relieve the adverse effects of oxidative stress via different pathways. Our results also confirmed that the interaction between MCLR and LAS was synergistic. Both toxicants in combination not only significantly inhibited seedling growth, but also increased the activities of superoxide dismutase and catalase, as well as the contents of glutathione. Furthermore, LAS dramatically enhanced the accumulation of MCLR in the plant, thus leading to a reduction in quality and yield and posing greater potential risk to humans via consumption of these edible plants.