•Combing usage of QuEChERS and DLLME for the determination of neonicotinoid residues in grains.•Smart role of water as extractant in QuEChERS and as external phase in DLLME.•Extraction relay using MeCN after water in QuEChERS and successive play of MeCN as dispersant in DLLME.•Comprehensive consideration of the single factor test and response surface method to optimize parameters.•Good sensitivity, precision, and applicability of the developed method for real grains samples. Monitoring neonicotinoid residues in grains is of significant interest for the proper assessment of pesticide exposure to human. The quick, easy, cheap, effective, rugged, and safe extraction method combined with dispersive liquid-liquid micro-extraction (QuEChERS-DLLME) was developed for extracting, purifying, and concentrating seven common neonicotinoid pesticides from the grains (rice, millet, and maize). Water and acetonitrile were used in tandem as extractants in QuEChERS, while water, acetonitrile, and trichloromethane in DLLME acted as the external phase, dispersant, and extractant, respectively. Comprehensive consideration of the single factor test and response surface method to optimize parameters including type and volume of extractants and dispersant. The evaluation showed that the QuEChERS-DLLME method held excellent linearity (R2 > 0.99). The limits of quantitation ranged from 0.003 to 0.08 µg kg−1 for the seven insecticides. The recoveries were in the range of 62–118%, and good reproducibility was obtained with a relative standard deviation below 15%.