The invention relates to the field of electric power industry information, and discloses a power plant safety management system and method based on two-dimensional code and an electronic key. The system comprises a plurality of two-dimensional code labels, an electronic key, a mobile terminal and a back-end server. Each two-dimensional code label is arranged on one power plant device, and includes corresponding identification information for the power plant device; the electronic key contains unlock information matching with the identification information in each of the two-dimensional code labels, and unlocks the power plant device when the unlock information matches the identification information; the mobile terminal is used to scan the two-dimensional code labels to obtain identification information and send the identification information to the electronic key for the matching of unlock information and the identification information; and the back-end server is used for sending the operation information corresponding to the power plant device to the mobile terminal during the matching of the unlock information and the identification information. The invention employs systematic, comprehensive mobile and integrated danger isolation mode to increase the security of the operation personnel in the power plant.