The invention provides a substation sequence control system and method with a control main station safety check function. The safety of sequence control is improved by the deployment of an anti-errorsecurity check workstation at a control main station and an information interaction manner proposed in the invention. According to the system, a sequence control module is deployed at a substation end, a centralized sequence control module and the anti-error security check workstation are deployed at a control main station end, a sequence control workstation is deployed at an operation and maintenance class station to which the substation belongs, the interaction is carried out through an existing network, the sequence control module at the substation end generates an operation ticket, after the check of the anti-error security check workstation of the control main station is passed, the sequence control module continues to perform a sequence control operation. According to the anti-errorsecurity check workstation of the control main station, according to error prevention logic between substations, the topology judgment and check are carried out based on a whole network, an error operation caused by operation information asymmetry between different stations and delayed communication report is avoided, and the safety of sequence control is improved.