BACKGROUND: Autophagy was a significant catabolic process which played a critical role in the maintenance of cellular homeostasis and viability in a stressed state. The dysregulation of autophagy was correlated with various diseases. The aim of our study was to develop a prognostic signature for papillary renal cell carcinoma (RCC). METHODS: First, 40 differently expressed genes related with autophagy (ARGs) were examined via high-throughput sequencing and large-scale databases. Then, functional enrichment analysis was performed to explore the biological attributes of these ARGs. The Cox proportional hazard regression hinted that four ARGs (, , and ) were significantly correlated with overall survival (OS). Thus, we got genes with prognostic value. Finally, a prognostic index (PI) was constructed. RESULTS: After identifying the 4 ARGs, we profiled our risk signature. Based on the PI we developed, papillary RCC patients were stratified into high-risk and low-risk groups. High-risk patients had significant shorter OS than low-risk patients (P<0.001) and the mortality of high scoring patients was higher than low scoring patients. Additionally, we explored the relationship between the 4 ARGs and clinical parameters and found that the expression of , and was correlated with clinicopathological features. CONCLUSIONS: Our study suggested that the four-gene signature was an independent prognostic factor which could act as a novel indicator for the prognosis of papillary RCC.