Based on the time-correlated leakage model and fuzzy random probability theory, a formula for calculating fuzzy random reliability of sealing performance of bolted flanged connections was derived. The optimization variables were defined according to the sensitivity analysis of design parameters on fuzzy reliability of sealing performance. A fuzzy reliability optimization design method of flange was investigated, in which both the tightness of bolted flanged connections and the strength of flange were taken into consideration. As an example, an integral welding necked pipe flange was designed according to the optimization design method proposed in this paper. The designed flange not only satisfies the requirements of flange strength and sealing reliability of connections, but also its weight is reduced by 16% compared with that prescribed in the standard.