Ultrasound is capable of noninvasive transcranial focusing and activating the targeted neurons in brain regions, receiving increasing attention. Ion channel, acting as a nano-ionic switch, enables to modulate the ion flow across cellular membranes and it is of importance to control the firing frequency of a neuron. In this article, we demonstrate the behavioral response of Caenorhabditis elegans (C. elegans) in response to ultrasound stimulation mediated by the activation of mechanical sensitive MEC-4 and MEC-6 ion channels. By specific mutation of MEC-4 and MEC-6 ion channels, mutant worms show a significant decrease in the percentage of reversal behavior (30% ± 10.5% and 10% ± 6.9%, respectively), compared with wild type (85% ± 8.2%). Furthermore, ALM and PLM neurons expressing MEC-4 and MEC-6 ion channels could be evoked directly by ultrasound stimulation, indicating MEC-4 and MEC-6 may pave a new way for sonogenetics.