It has been well reported that the Si substituted hydroxyapatite has shown improved osteogenic properties. However, the underlined mechanisms remain to be elucidated. In this study, we have prepared nanostructured Si-HA coatings (Si: 0.8-4.8 wt%) using a liquid precursor plasma spraying process, and characterized the physiochemical properties of the Si-HAs, including the zeta potential, surface energy and surface roughness. Bovine serum albumin (BSA), fibronectin (FN), lysozyme (LSZ) have been used to examine the effect of the Si content on the protein adsorption behaviour of Si-HA, and its correlation with the physiochemical properties has been systematically analyzed. The adsorption of BSA and LSZ on the surface of the Si-HA increased with the silicon content, whereas a different adsorption behavior of FN has been observed. To further examine the adsorption behavior and the cellular responses of Si-HA, mesenchymal stem cell (MSC) responses to the Si-HA coatings have been examined under serum-free culture conditions, with pre-adsorption of three different proteins (BSA, FN and collagen I). The results indicated that, the pre-adsorption of BSA and collagen I promoted the proliferation of MSCs on Si-HA coatings, whereas the FN pre-adsorption on Si-HA had no obvious effect on the MSC proliferation. Overall, the results suggested direct correlation of Si substitution, protein adsorption behavior and MSC proliferation, providing new insight on the underlined mechanism of improved osteogenic properties of Si-HA.