The rapid development in IT and OT system makes interactions among themselves and with humans immerse in the information flows from the physical to cyberspace. The traditional view of cyber-security faces challenges of deliberate cyber-attacks and unpredictable failures. Hence, cyber resilience is a fundamental property that protects critical missions. In this paper, we presented a mission-oriented security framework to establish and enhance cyber-resilience in design and action. The definition of mission-oriented security is given to extend CIA metrics of cyber-security, and the process of mission executions is analyzed to distinguish the critical factors of cyber-resilience. The cascading failures in inter-domain networks and false data injection in the cyber-physical system are analyzed in the case study to demonstrate how the mission-oriented security framework can enhance cyber resilience.