Cats positive effects on their owners' physiological and psychological health, including improved mood and activation of the human prefrontal cortex and inferior frontal gyrus in the brain. However, the association between the health benefits provided by cat ownership and the characteristic behaviors and reactions of cats is unclear. We recruited 29 participants to measure human prefrontal cortex activity, using functional near-infrared spectroscopy, during interactions with a cat. After the experiments, participants subjectively responded to a questionnaire regarding success rates for interactions with the cat, and completed the Self-assessment Manikin-a scale used to measure emotion. Interactions comprised eight types in four categories (touch, play, train, and feed). This study showed that interactions with a cat significantly activated the prefrontal cortex, regardless of interaction type. During training, the integral values of oxygenated hemoglobin in the left inferior frontal gyrus were the highest in all the interaction categories; however, success rates were lower than in the touch and feed interactions. Regarding the Self-assessment Manikin scores, all interaction categories showed a positive correlation between success rate and valence score, especially in the train and play interactions than in the touch and feed interactions. These results indicate that interactions with a cat activate the prefrontal cortex in humans, including the inferior frontal gyrus region. Moreover, cats' autonomous behaviors and reactions positively influenced the participants. The characteristic temperament of cats may be a key factor influencing the health benefits of owning cats.