A fundamental issue in neuroscience is to understand the structural substrates of neural activities. Intrinsic brain activity has been increasingly recognized as an important functional activity mode and is tightly linked with various cognitive functions. Structurally, cognitive functions have also shown a relation with brain volume/size. Therefore, an association between intrinsic brain activities and brain volume/size can be hypothesized, and brain volume/size may impact intrinsic brain activity in human brains. The present study aimed to explicitly investigate this brain structure-function relationship using two large independent cohorts of 176 and 236 young adults. Structural-MRI was performed to estimate the brain volume, and resting-state functional-MRI was applied to extract the amplitude of low-frequency fluctuations (ALFF), an imaging measure of intrinsic brain activity. Intriguingly, our results revealed a robust linear correlation between whole-brain size and ALFF. Moreover, specific brain lobes/regions, including the frontal lobe, the left middle frontal gyrus, anterior cingulate gyrus, Rolandic operculum, and insula, also showed a reliable, positive volume-ALFF correlation in the two cohorts. These findings offer direct, empirical evidence of a strong association between brain size/volume and intrinsic brain activity, as well as provide novel insight into the structural substrates of the intrinsic brain activity of the human brain.