[Objectives]  The new insecticide sulfoxaflor is widely used to control insect pests but little is known about its effects on honeybees (Apis mellifera ligustica). The sublethal effects of sulfoxaflor on the expression of six detoxification (CYP9Q1, CYP9Q2, CYP9Q3, CYP9S1, CYP6AS5 and CYP4G11), four immune (Abaecin, Defensin, Hymenoptaeci and Apidaecin), and three memory (PKA, GluRA and NMDAR1), related genes in honeybees was investigated. [Methods]  (1) The LD₅₀ value of sulfoxaflor to honeybees was assessed using the “oral-feeding tube” method. (2) Changes in the expression of six detoxification, four immune, and three memory related genes were measured 48 h after bees had been fed sublethal doses (1/3 LD₅₀ and 1/10 LD₅₀) of sulfoxaflor. [Results]  (1) The LD₅₀ value of sulfoxaflor to honeybees was 0.099 μg/bee. (2) Exposure to 1/3 LD₅₀ of sulfoxaflor significantly inhibited Abaecin and Defensin expression in honeybees (P < 0.05), but up-regulated the expression of PKA, NMDAR1, GluRA, CYP9Q2 and CYP9Q3 (P < 0.05). The expression levels of Hymenoptaecin, Apidaecin, CYP6AS5 and CYP4G11 in both treatment groups were significantly higher than in the control group. Sulfoxaflor did not, however, affect the expression of CYP9Q1 and CYP9S1. [Conclusion]  Sulfoxaflor could potentially affect the detoxification, immune and memory systems of honeybees. These results provide a basis for further exploring the complex molecular interactions between sulfoxaflor and honeybees.