Hydrogen Induced Stress Cracking (HISC) is a phenomena related with metals, with potentially severe consequences when utilizing Duplex / Super Duplex stainless steels in subsea equipment exposed to Cathodic Protection (CP). In general, the three conditions need to be present: hydrogen source (CP), susceptible material (Duplex/Super Duplex stainless steel) and high stresses/strains. The third one can be related with loads, calculation promises and parts design in general (for example risers). The designing rules to minimize the risk of HISC failure are still in development and the latest state of art is presented in DNVGL-RP-F112 June 2018 edition. The Compact Flange (CF) is much lighter and more robust connection than standard ASME or API types as the CF design methodology is based on plastic capacity which is presented in the ISO-27509 code. However, ISO standardization covers only topside applications (with IX seal ring type), pressure class range up to CL2500 and simplified face angles methodology. The ISO-27509 flanges are not HISC proven. Therefore, to deal with HISC requirements and subsea conditions the SPO-S (Subsea) flange series with HX seal ring type was defined and type approved by DNVGL based on extensive FEA documentation, testing and field experience. The SPO-S range has, currently, only HISC compliant designs for the 5K, 7.5K, 10K and 15K flange ranges. For the projects where the Duplex / Super Duplex flanges are used subsea with CP, consideration for HISC still must be addressed. For such cases, the process is not straight forward and often many FEA rounds are needed depending on the engineer’s experience and project related restrictions. The process is time consuming and every decision reflects many aspects to finalize the design. Genetic Algorithms (GA) are a good optimization tools to use in such situations, because at the end, the engineer will only get few design propositions to choose from, and the process itself, is highly automated. In the following paper the results for HISC optimized CF flange connection will be presented and compared with standard ISO-27509 flange design. The GA optimization steps and designing process will also be presented in the same example. Commercial FEA code ANSYS will be used for calculations based on parametrical model and GA implemented by APDL scripting. The following optimization method is already in use for HISC related projects.