The titanium implant surface topography optimization for improving osseointegration has been performed for many years, whereas understanding the mechanisms of topography-induced osteogenic differentiation is still insufficient. In this study, the micro/nano-textured topography was created on titanium implant surface by acid etching and anodization. The MC3T3-E1 cells were incubated with different surfaces and the RNA sequencing technique was performed to obtain the transcriptomic information, which suggested the enrichment at "membrane" and "organelle" (GO) as well as "Calcium signal pathway" (KEGG). Consequently, a special attention was paid to the store-operated calcium entry (SOCE) mediated by Orai1 at ER-PM contact site. By fluorescence staining and western blot, it was confirmed that the Orai1 was upregulated on the micro/nano-textured titanium surface, which was correlated to the enhanced osteogenic differentiation induced by topography. Further experiments indicated that the CaMKII/ERK1/2 pathway was involved in. This research is the first time giving a comprehensive transcriptomic information of osteoblasts on micro/nano-textured topography and may provide deeper insight into the interaction between biomaterials and host.