We introduce a non-invasive approach for optogenetic regulation in biological cells through highly scattering skull tissue using wavefront shaping. The wavefront of the incident light was systematically controlled using a spatial light modulator in order to overcome multiple light-scattering in a mouse skull layer and to focus light on the target cells. We demonstrate that illumination with shaped waves enables spatiotemporal regulation of intracellular Ca(2+) level at the individual-cell level.