A MOF-on-MOF composite (PCN-222@PCN-134) was synthesized by seed epitaxial growth method and applied as sorbent to extract sulfonamides (SAs) in different sample matrices. Using PCN-222@PCN-134 as sorbent, a dispersive solid-phase extraction was developed to clean-up and preconcentration of SAs prior to HPLC-DAD analysis. The linear range of the method are achieved between 0.1 and 200 ng/mL, and the limits of detection are in the range of 0.03–0.27 ng/mL. Comparison with pristine MOFs, the performance of PCN-222@PCN-134 composite is significantly improved. The enrichment factors are obtained in the range of 254–333. The adsorption kinetics and adsorption isotherms are in accordance with pseudo-second-order and Langmuir models, respectively. The spiked recovery of real samples including egg and urine are between 76.4 and 120.1 % with relative standard deviation not higher than 12.1 %. After 14 times of use, the recovery rate of sorbent to SAs is still above 80 %. This work demonstrates that PCN-222@PCN-134 possesses excellent extraction performance to SAs, which can be used to clean-up and preconcentration of trace SAs in different sample matrices, such as egg and urine.