Depression is a common non-motor system symptom in patients with multiple system atrophy (MSA). Its pathogenesis is unknown. Multimodal functional magnetic resonance imaging (fMRI) is the main tool to explore the mechanism of pure depression and other diseases with depressive symptoms. Applications of fMRI on patients with MSA in accompanied with depressive symptoms is expected to reveal the difference to the MSA-involved depression mechanism different to the pure depression-involved brain network. Our results found altered secondary network in MSA patients with depression and provided a new idea for determination on treatments to MSA with depression. This study provided neuroimaging evidence for a clinical understanding of non-pure depression and possible reference for treatment measures.