Autophagy plays a vital role in cerebral ischemia and may be a potential target for developing novel therapy for stroke. In this study, we constructed an autophagy-related pathway network by analyzing the genes related to autophagy and ischemic stroke, and the risk genes were screened. Two autophagy-related modules were significantly up-regulated and clustered to influence cerebral ischemia. Besides, three key modular genes (NFKB1, RELA, and STAT3) were revealed. With 5-fold cross validation, the ROC curves of NFKB1, RELA, and STAT3 were 0.8256, 0.8462, and 0.8923. They formed a complex module and competitively mediated the activation of autophagy in cerebral ischemia. In conclusion, a module containing NFKB1, RELA, and STAT3 mediates autophagy, serving as a potential biomarker for the diagnosis and therapy of ischemic stroke.