Clarifying the intrinsic mechanisms of acupuncture's clinical effects has recently been gaining popularity. Here, we choose the Siguan acupoint (a combination of bilateral LI4 and Liv3) and its sham point to evaluate multiacupoint specificity. Thirty-one healthy volunteers were randomly divided into real acupoint (21 subjects) and sham acupoint (10 subjects) groups. Our study used a single block experimental design to avoid the influence of posteffects. Functional magnetic resonance imaging data were acquired during acupuncture stimulation. Results showed extensive increase in neuronal activities with Siguan acupuncture and significant differences between stimulation at real and sham points. Brain regions that were activated more by real acupuncture stimulation than by sham point acupuncture included somatosensory cortex (the superior parietal lobule and postcentral gyrus), limbic-paralimbic system(the calcarine gyrus, precuneus, cingulate cortex, and parahippocampal gyrus), visual-related cortex (the fusiform and occipital gyri), basal ganglia, and the cerebellum. In this way, our study suggests Siguan may elicit specific activities in human brain.