Loneliness results from lacking satisfied social connections. However, little is known how trait loneliness, which is a stable personal characteristic, is influenced by different types of social support (i.e. emotional and instrumental support) through the brain activity associated with loneliness. To explore these questions, data of resting-state functional magnetic resonance imaging (R-fMRI) of 92 healthy participants were analyzed. We identified loneliness-related brain regions by correlating participants' loneliness scores with amplitudes of low-frequency fluctuation (ALFF) of R-fMRI data. We then conducted mediation analyses to test whether the negative relation between each type of social support and loneliness was explained via the neural activity in the loneliness-related brain regions. The results showed that loneliness was positively related to the mean ALFF value within right inferior temporal gyrus (ITG). In addition, the negative relation between emotional support and loneliness was explained by a decrease in the spontaneous neural activity within right ITG but this pattern was not observed for instrumental support. These results suggest the importance of social information processing on trait loneliness and highlight the need to differentiate the functions of different types of social support on mental health from a neural perspective.