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In this study, we examined the expression of 11 cytokines in liver and serum of C57BL/6 mice upon single or co-exposed to Aflatoxin B1 and Microcystin-LR at low-dose and sub-chronic conditions. The objective is to elucidate the potential combined hepatotoxic effects induced by AFB1+MC-LR, and we aim to provide references for further immune impacts in the liver. Luminex-based cytokine examination was applied, and we found that most of the cytokine expression increased with time. The level of IL-18, GM-CSF, IFN-γ, IL-1β and IL-4 in the liver showed a significant rise. However, some cytokines (IL-13) showed an upward trend after being suppressed during the middle stage of exposure. The level of IFN-γ and IL-12p70 generally represented the immune response in the combined exposure group. Conclusionally, there are many uncertainties due to sub-chronic and low-dose exposure. Therefore, the occurrence of subsequent irreversible liver injury and liver cancer is a probabilistic event.