A printed circuit board (PCB) acts as backbone of any electronic system hardware by providing mechanical support and electrical connections to its active and passive components. Traditionally, the PCB of a system has been considered trusted and robust during field operation. However, there are numerous recent reports on physical tampering of PCB in the field for malicious alteration of its functionality (e.g. adding/replacing a component through soldering, snooping a trace, and bypassing a connection). Through such alteration, an adversary can leak secret information from PCB or bypass security protection implemented in a system. This paper presents a novel approach to detect a tampering in a PCB after it is deployed and to actively prevent system operation when a tampering is detected. To our knowledge, this is the first report on active protection against PCB tampering in field. The proposed autonomous monitoring and prevention can enable active defense against physical tampering of electronic hardware, thus maintaining the integrity of a system against various security issues arising from such tampering.