A dissolvable layered double hydroxide-based solid-phase extraction combined with high-performance liquid chromatography was developed for the analysis of minocycline, oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline and doxycycline in milk samples. In situ formation of the layered double hydroxide was achieved by the addition of MgCl2-AlCl3 solution to alkaline deproteinized milk. The analytes were efficiently extracted by the Mg/Al layered double hydroxide. After centrifugation, the co-precipitates were dissolved in 0.1 mol L-1 Na2EDTA-McIlvaine buffer prior to HPLC analysis. Under optimized conditions, the method achieved low detection limits of 0.414-0.986 μg L-1 and quantification limits of 1.38-3.29 μg L-1, and good recoveries of 93.5-100% with intra- and inter-day RSDs of 0.498-4.08% and 1.23-10.0%, respectively. This method is convenient, accurate, sensitive, rapid, cost-effective, eco-friendly, and suitable for the determination of seven tetracycline antibiotics in milk samples.