Although self-other behavioral differences in decision making under risk have been observed in some contexts, little is known about the neural mechanisms underlying such differences. Using functional magnetic resonance imaging (fMRI) and the cups task, in which participants choose between risky and sure options for themselves and others in gain and loss situations, we found that people were more risk-taking when making decisions for themselves than for others in loss situations but were equally risk-averse in gain situations. Significantly stronger activations were observed in the dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI) when making decisions for the self than for others in loss situations but not in gain situations. Furthermore, the activation in the dmPFC was stronger when people made sure choices for others than for themselves in gain situations but not when they made risky choices, and was both stronger when people made sure and risky choices for themselves than for others in loss situations. These findings suggest that gain-loss situation modulates self-other differences in decision making under risk, and people are highly likely to differentiate the self from others when making decisions in loss situations.