Over-voltage and over-current protection are two forms of over-voltage and over-current protection sequences of intrinsic safety power supply. In order to study the influence of different protection sequence forms on safety performance of intrinsic safety power supply, an equivalent model of spark discharge of intrinsic safety power supply was established, and essential safety performance factors affected the selection of the protection sequences were determined. The protection performance of two protection sequences was compared and studied when happened over-voltage, over-current and over-voltage over-current. The research results show that in the design of intrinsic safety power supplies, the selection of over-voltage and over-current protection sequence is not random and arbitrary, but there are principles to follow: the type of over-voltage protection circuit determines the sequences of over-voltage and over-current protection of intrinsic safety power supplies. In design, the first step is determining the type of over-voltage protection circuit, if the type of over-voltage protection circuit is short circuit type, protection circuit of intrinsic safety power should be designed to protection sequences of over-current-over-voltage, otherwise it should be designed as over-voltage and over-current protection sequence, the protection circuit of the over-voltage and over-current protection sequence has a shorter turn-off time, the protection effect is better and the safety performance of the intrinsic safety power supply is higher.