Male urethral stricture disease (USD) is characterized by scar formation, whose molecular mechanism is still lack. In this study, we performed comprehensive proteomic landscape of USD with 12 scar tissues and 5 matched normal adjacent tissues (NATs). Comparative analysis disclosed the ECM signaling and complement cascade were overrepresented in the scar tissues, in which COL11A1, CNN2, and CD248 would play positive impacts.