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In this study, a statistical experimental design method (the Taguchi method with L9 orthogonal array robust design) was performed to optimize experimental conditions such that to maximize the Nusselt number of Al2O3-water nanofluids in a double tube counter flow heat exchanger. The controllable factors were selected at three sets of conditions including temperature (45, 55, and 65℃), concentration (0, 0.05, and 0.15 vol.%), and flow rate (7, 9, and 11 l/min) of the nanofluid. Analysis of the obtained results revealed that the flow rate plays a key role in the Nusselt number of nanofluid with 63.541%. The optimal levels were defined for the three factors including the nanofluid concentration of 0.15 vol.%, the nanofluid temperature of 65℃,and the nanofluid flow rate of 11 l/min. The predicted Nusselt number of nanofluid under these conditions was 322.633. The confirmation test was also performed at the optimal conditions, by which good consistency was found between the experimental and the predicted results.