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Abstract Uncertainties in ocean-mixing parameterizations are primary sources for ocean and climate modeling biases. Due to lack of process understanding, traditional physics-driven parameterizations perform unsatisfactorily in the tropics. Recent advances in the deep-learning method and the new availability of long-term turbulence measurements provide an opportunity to explore data-driven approaches to parameterizing oceanic vertical-mixing processes. Here, we describe a novel parameterization based on an artificial neural network trained using a decadal-long time record of hydrographic and turbulence observations in the tropical Pacific. This data-driven parameterization achieves higher accuracy than current parameterizations, demonstrating good generalization ability under physical constraints. When integrated into an ocean model, our parameterization facilitates improved simulations in both ocean-only and coupled modeling. As a novel application of machine learning to the geophysical fluid, these results show the feasibility of using limited observations and well-understood physical constraints to construct a physics-informed deep-learning parameterization for improved climate simulations.