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The ruthenium-doped titanium dioxide (TiO2:Ru) sensing films were deposited on silicon substrates by sputtering and applied in pH sensors based on separative extended-gate field effect transistor (SEGFET). The Taguchi method with L18 (21×37) orthogonal arrays and signal-to-noise (S/N) ratio were employed to study the performance characteristics. It was evaluated in terms of sensitivity to determine the optimal combination of the parameters. After Taguchi analysis, heat treatment temperature and annealed time were the most influencing parameters on the sensitivity of pH sensor. After verification of the experiments, the sensitivity of pH sensor is high (56.1~60.9 mV/pH, satisfy Nernstian response), stable (0.9987). Heat treatment temperature is controlled about 400°C can reach Nernstian response. Furthermore, super-Nernstian response could be attained when the temperature is controlled about 600°C.