Background: Many studies have found an interesting issue in the Internet gaming disorder (IGD): males are always observed to be the majority. However, there are little research to exploring the differences in the neural mechanisms between males and females in decision-making process among people with IGD. Therefore, explore the reward/loss processing between different gender with IGD could help in understanding the underlying neural mechanism of IGD. Methods: Data from functional magnetic resonance imaging (fMRI) were collected from 111 subjects (IGD: 29 males, 25 females; recreational internet game user (RGU): 36 males, 21 females) while they were performing a card-guessing task. We collected and compared their brain features when facing the win and loss conditions in different groups. Results: For winning conditions, IGD group showed hypoactivity in the lingual gyrus than RGU group, male players showed hyperactivity in the left caudate nucleus, bilateral cingulate gyrus, right middle frontal gyrus (MFG), right precuneus and inferior parietal lobule relative to the females. And significant sex-by-group interactions results showed higher brain activities in the thalamus, parahippocampal gyrus and lower brain activities in Inferior frontal gyrus (IFG) were observed in males with IGD than females. For losing conditions, IGD group showed hypoactivity in the left lingual gyrus, parahippocampal gyrus and right anterior cingulate cortex (ACC) compared to the RGU group, male players showed hyperactive left caudate nucleus and hypoactive right middle occipital gyrus relative to females. And significant sex-by-group interactions results showed that compared to females with IGD, males with IGD showed decreased brain activities in the IFG and lingual gyrus. Conclusions: First, there appeared to be no difference in reward processing between the IGD and RGU group, but IGD showed less sensitivity to loss. Secondly, male players showed more sensitivity to rewards and less sensitivity to losses. Last but not least, males and females showed opposite activation patterns in IGD degree and rewards/losses processing. And male IGD subjects are more sensitive to reward and less sensitive to loss than females, which might be the reason for the gender different rates on IGD. © 2020 The Author(s).