Hand, foot, and mouth disease (HFMD), usually a self-limiting illness for young children, could cause a significant burden for parents because it can take up to 1–2 weeks for a sick child to recover. We conducted a two-wave longitudinal study over one summer peak season (May–July 2014) of HFMD to examine parents’ HFMD-related risk perceptions and protective responses. In total, 618 parents with at least one child aged ⩽12 years, recruited using randomly-dialled household telephone calls completed the baseline survey interview, 452 of whom subsequently completed the follow-up survey. Around two-thirds of participants perceived the chance of their child being infected by HFMD was ‘zero/very small/small’ but the likelihood of being hospitalized once infected was ‘somewhat likely/likely/very likely’. At follow-up, 82% reported washing child's hands frequently (Hygiene), 16% would keep their child away from school if HFMD cases were identified in school (Distancing) and 23% were ‘very likely/certainly’ to take the child for HFMD vaccination if available (Vaccination). Anticipated regret was consistently the strongest predictor for Hygiene (OR 3.34), and intention of Distancing (OR 2.58) and Vaccination (OR 3.16). Interventions focusing on anticipated regret may be effective to promote protective behaviour against HFMD among parents for their children.