Antibiotics are frequently used in aquaculture as feed additives and finally enter the marine environment that can pose potential threat to humans. In this study, magnetic molecularly imprinted nanocomposites were prepared by surface imprinting and applied as selective sorbents for specific capture of doxycycline. A multivariate approach based on response surface methodology with Box-Behnken design was adopted to optimize the dispersive solid-phase extraction of doxycycline from marine sediment. Three key parameters, including adsorbent amount and type of washing/eluting solvent, were screened. Under optimum conditions, the limit of detection was 0.03μgg-1 with good linearity from 0.5 to 20μgg-1 followed by HPLC detection. Finally, two sediment samples were analysed and satisfactory recoveries between 90.60% and 93.76% were obtained with acceptable relative standard deviations (≤4.12%), suggesting a promising applicability of the developed method for efficient extraction and sensitive quantification of antibiotics in complex marine environmental matrix.