The invention relates to a preparation method of a lamellarin derivative. The preparation method comprises the following steps: adding an organic solvent into reaction substrates which are tetrahydroisoquinoline, alpha-bromo-aromatic ethanone and a nitro vinyl aromatic compound; then adding one or more copper compound catalysts, carrying out a tube sealing reaction at a reaction temperature of 0-150 DEG C for 24 h to prepare a product mixture through one-step synthesis; and after the reaction is finished, filtering the obtained product mixture to remove the copper compound(s), and concentrating and separating the obtained filtrate to obtain the lamellarin derivative. According to the method, one-step synthesis reaction is adopted to prepare the lamellarin derivatives, the initial raw materials and the catalysts are cheap and easily available, reaction conditions are mild, the operation is simple, the substitution type of functional groups is less limited, and the atom utilization rateis high.