A simple, convenient, and economic self-assembly miniaturized syringe assisted extraction (mini-SAE) using poly (hydroxyethyl methacrylate) polymer (PHEMA) as sorbent coupled with liquid chromatography was proposed for rapid screening of sulfadiazine (SD) and sulfamonomethoxine (SMM) in milk. The water-compatible PHEMA was synthesized by reversible addition-fragmentation chain transfer precipitation polymerization using trithiocarbonate as chain transfer agent and methanol–water system as reaction medium. The obtained PHEMA sorbent showed good affinity to sulfonamides and was successfully applied as a special sorbent for a mini-SAE device for simultaneous extraction and isolation of SD and SMM in milk samples. Under the optimum condition, good linearity was obtained in a range of 7.0–700ngg−1 (r≥0.9995) and the average recoveries of SD and SMM at three spiked levels were ranged from 85.6 to 100.3% with the relative standard deviations (RSD) ≤6.5%. The presented PHEMA-mini-SAE protocol could be potentially applied as an alternative tool for analyzing the residues of SAs in complicated biological samples.