A variety of antifungals are used for topical application. Some of them have been reported to cause adverse effects, such as pain and irritation. However, the molecular basis for these effects remains unknown. Nociceptive TRPV1 and TRPA1 are mainly expressed in sensory neurons and act as sensors for irritant chemicals. Here, we investigated whether these channels are involved in the painful adverse effects of topical antifungals. Among them, isoconazole, econazole, miconazole, clotrimazole, and ketoconazole as imidazoles; liranaftate as thiocarbamates; terbinafine as allylamines; amorolfine as morpholines; and butenafine as benzylamines were used. All the drugs used evoked [Ca²⁺]_i increases in TRPA1-expressing HEK293 cells. At high concentrations, many drugs induced [Ca²⁺]_i increases non-specifically, but clotrimazole, ketoconazole, and liranaftate evoked TRPA1-specific [Ca²⁺]_i and current responses. Clotrimazole and ketoconazole also evoked [Ca²⁺]_i and current responses in TRPV1-expressing HEK293 cells. In mouse sensory neurons, liranaftate elicited [Ca²⁺]_i increases being diminished by a TRPA1 blocker or the deletion of the TRPA1-gene. [Ca²⁺]_i responses to ketoconazole and clotrimazole were suppressed by the blockade of both TRPA1 and TRPV1. These results suggest that the pain and irritation induced by topical antifungals may be due to the activation of nociceptive TRPA1 and/or TRPV1 channels. Therefore, the concomitant use of these channel inhibitors is expected to reduce the adverse effects of these topical antifungals.