The invention relates to the field of automatic control and discloses a control device and method for safety protection of a boiler in an oxygen-enriched combustion system. The control device comprises a monitoring module and a control module. The monitoring module is used for monitoring the running state of important auxiliary equipment for the boiler in the oxygen-enriched combustion system and then monitoring oxygen concentration, pressure and temperature in an air separation unit, an oxygen delivery pipeline, and an oxygen-injection position of a combustion and smoke-wind subsystem and sending running state, oxygen concentration, pressure and temperature of the important auxiliary equipment to the control module. The control module is used for determining whether running state of the important auxiliary equipment is abnormal or not and making comparisons between monitored oxygen concentration, pressure and temperature and respective setting values hereof. A tripping signal for main fuel of the boiler is emitted in either case as follows: abnormal running state of the important auxiliary equipment, and the fact that any of monitored oxygen concentration, pressure and temperature is greater than the setting value thereof. The tripping signal for main fuel of the boiler enables fuel supply of the boiler and oxygen delivery of the oxygen-enriched combustion system to be cut off and prompts related important auxiliary equipment to trip in a linkage mode. The control device and method for safety protection of the boiler in the oxygen-enriched combustion system is capable of protecting safety of the oxygen-enriched combustion system.