Hiccups or singulata are rhythmic involuntary movements of the diaphragm, caused by a variety of conditions that interfere with the functions of the nerve nuclei in the medulla and supra-spinal hiccup center. Although neurotransmitters and receptors involved in the pathophysiology of hiccups are not defined well, dopamine has been considered to play an important role. In some cases, chlorpromazine or other antipsychotics are used for the treatment of intractable hiccups but their efficacy is often limited. This report involves an 18-year-old patient who experienced two episodes of intractable hiccups triggered by stress, which lasted for weeks or even months. In both episodes, haloperidol was initially used, but there was no significant effect. In contrast, risperidone, the second-generation antipsychotic that possesses a dopamine-serotonin antagonist property, completely abolished the hiccups 6 hours after administration. This is one of few case reports in which two antipsychotics were challenged for a single patient with hiccups, and the effects of the drugs were obviously different. Our finding suggests that, in addition to dopaminergic system, the serotonergic systems may be involved in the pathophysiology of some hiccup cases and that the serotonin-acting antipsychotics such as risperidone should be considered as a choice in the drug treatment of intractable hiccups.