Here, ultraviolet-visible (UV-Vis) spectroscopy, zeta potential, and chemometrics approaches are used to study the interactions between alginate (Alg) and bovine serum albumin (BSA), respectively as polyanion and polycation. The optimum conditions are obtained at Alg/BSA mixing ratio of 1:4 and pH 4 due to the appropriate complexation between Alg and BSA polyelectrolytes. The layer-by-layer (LBL) assembled (Alg/BSA) 7 @SiO 2 nanocapsules are prepared by repeated deposition of Alg and BSA polyelectrolytes on the surface of SiO 2 -NH 2 nanoparticles. The dried (Alg/BSA) 7 @SiO 2 nanocapsules are dispersed in NH 4 F/HF buffer solution to remove the silica core and (Alg/BSA) 7 hollow capsules are achieved. (Alg/BSA) 7 hollow capsules are characterized by Fourier-transform infrared (FT-IR), scanning electron microscopy (SEM) with energy dispersive x-ray analysis (EDX), thermal gravimetric analysis (TGA), and zeta potential analyses. The sensitivity of the hollow capsules to pH is investigated utilizing UV-Vis spectroscopy. Evaluation of cytotoxicity analysis for (Alg/BSA) 7 @SiO 2 nanocapsules using the MTT assays on Michigan Cancer Foundation-7 (MCF-7) cells shows no toxicity effect. The (Alg/BSA) 7 hollow capsules have suitable potential as carriers for drug delivery due to their biocompatibility and bioavailability. Betamethasone disodium phosphate (BSP) is loaded on the (Alg/BSA) 7 hollow capsules due to biocompatibility and shows a controlled releases profile at pH 7.4. IntroductionLots of researches have been done to construct artificial capsules similar to biological capsules. Efforts in this area have led