The gas pipelines are a significant part of energy transportation pipelines and are recognized as a vital component of societal infrastructure. Earthquake-induced damage to gas pipelines can have severe disastrous humanitarian, social, economic, and ecologic consequences. To mitigate these consequences, one effective approach is to carefully design gas pipeline routes, considering the seismic hazard of the region. Conventional gas pipeline design methods consider only minimum distances from faults and fails to account for seismic potential of faults. This paper introduces a methodology that integrates seismic risk assessment into the gas pipeline route design process. Seismic risk is performed using the HAZUS method, and pipeline routing optimization is accomplished through the application of a metaheuristic algorithm within a GIS-based framework. The methodology is applied in to three gas pipeline routing problems within the high seismic region of southern Iran. The results are then compared with conventional approaches, considering factors such as route length, seismic risks, and seismic damage costs. The findings demonstrate the proposed method effectiveness in mitigating seismic risks related to gas pipeline. The proposed method enables a quantitative and direct incorporation of seismic risk into gas pipeline routing, marking a departure from the qualitative methods presently in use.