When humans perceive a sensation, their brains integrate inputs from sensory receptors and process them based on their expectations. The mechanisms of this predictive coding in the human somatosensory system are not fully understood. We fill a basic gap in our understanding of the predictive processing of somatosensation by examining the layer-specific activity in sensory input and predictive feedback in the human primary somatosensory cortex (S1). We acquired submillimeter functional magnetic resonance imaging data at 7T (n = 10) during a task of perceived, predictable, and unpredictable touching sequences. We demonstrate that the sensory input from thalamic projects preferentially activates the middle layer, while the superficial and deep layers in S1 are more engaged for cortico-cortical predictive feedback input. These findings are pivotal to understanding the mechanisms of tactile prediction processing in the human somatosensory cortex.