A series of combinatorial optical screening analysis was operated, first for the selection of metals adequate for the ternary Ru-based catalyst and later for the selection of the optimized compositions with high performance towards ORR. Among the binary Ru-based catalysts (Co, Cu, and etc), Co and Se exhibit higher performance towards ORR compared to other binary Ru-based combinations. To investigate a possible synergic effect from the selected metals, the ternary Ru-based combinatorial optical screening was preceded. The optimum composition towards ORR for ternary Ru-Se-Co based catalyst was chosen at 73: 12: 15 = Ru: Se: Co at. % (named RSC-1). The RSC-1 catalyst measured a current density of-1.28 mAcm-2 at 0.75 V (vs. RHE), which was about 5 times than that of Ru/C (-0.26 mAcm-2). The mass activity of RSC-1 (12.20 mAmg-1) had an enhanced performance of about 6.8 times than that of Ru/C (1.78 mAmg-1) at 0.75 V (vs. RHE). A synergic effect between the repulsion of oxy-species on the Ru atoms by Se and the electron modification by Co, at adequate amounts of Co and Se in the ternary Ru-Se-Co based catalyst, could have induced the enhanced ORR performance of the RSC-1 catalyst.