The excitability of brainstem circuitries mediating defensive blinking in response to abrupt sensory inputs is continuously modulated by cortical areas, e.g., the hand-blink reflex (HBR), elicited by intense electrical median nerve stimulation, is enhanced when the stimulated hand is close to the face, with the behavioural purpose to optimize self-protection from increased threat. Here we investigated whether such cortically mediated HBR facilitation can be influenced by prepulse inhibition (PPI), which is known to occur entirely at the subcortical level. Twenty healthy volunteers underwent HBR recordings in five experimental conditions. In conditions 1 and 2, the stimulated hand was held either near (1) or far (2) from the face, respectively. In conditions 3 and 4, stimulation of the hand near the face was preceded by a peri-liminal prepulse to the index finger of the contralateral hand held either near (3) or far from the face (4). In condition 5, participants self-triggered the stimulus eliciting the HBR. We observed a reproducible HBR in 14 out of 20 participants and measured onset latency and area of the HBR in orbicularis oculi muscles bilaterally. HBR area decreased and latency increased in condition 2 relative to condition 1; HBR area decreased and latency increased markedly in condition 3, and somewhat less in condition 4, relative to conditions 1 and 2; self-stimulation (condition 5) also suppressed HBRs, but less than prepulses. These findings indicate that PPI of the HBR is more robust than the cognitive modulation exerted by top-down cortical projections. Possibly, an attentional shift to a prepulse may serve to reduce blinking in response to perturbation when it is convenient, in a given situation, not to interrupt ongoing visual processing.