Lateral flow immunoassay (LFIA) is an affordable and rapid technique for detecting veterinary drugs such as sulfonamides (SAs). However, balancing accuracy, sensitivity, and convenience remains a challenge. To address this, a microfluidic chip-based LFIA utilizing a zirconium-based organic framework, PCN-222@liposome, was developed to simultaneously detect four Sas: sulfamethizole, sulfamethoxazole, sulfamethoxydiazine, and sulfathiazole, with both colorimetric and fluorescent dual-signal detection. In this study, PCN-222 was modified with liposomes to enhance its biocompatibility and water solubility. Characterization through scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, and Fourier-transform infrared spectroscopy, confirmed the successful incorporation of liposomes with PCN-222. Under optimized conditions, the PCN-222@liposome-LFIA demonstrated high sensitivity, with detection limits ranging from 0.01 to 0.05 μg/L using fluorescent signals-10 times more sensitive than conventional gold nanoparticle-based LFIA. Finally, the PCN-222@liposome-LFIA integrated with the microfluidic chip successfully detected the four SAs in chicken, shrimp, and milk samples, with recoveries ranging from 89.65 % to 118.78 %. This study presents a simple, sensitive, and efficient method for the rapid detection of veterinary drug residues.