Palm oil mill effluent (POME) is a type of wastewater posing large problems when discharged in the environment. Yet, due to its high nutrient content, POME may offer opportunities for algal growth and subsequent harvesting of high-value products. The marine diatom Phaeodactylum tricornutum is a potential feedstock diatom for bioactive compounds such as the carotenoid fucoxanthin, which has been shown to have pharmaceutical applications. The aim of this paper was to evaluate the growth and fucoxanthin productivity of P. tricornutum grown on POME, as a function of light intensity, temperature, salinity, and nutrient enrichment. High-saturating irradiance (300 μmol photons m −2 s −1) levels at 25°C showed highest growth rates but decreased the fucoxanthin productivity of P. tricornutum. Box-Behnken response surface methodology revealed that the optimum fucoxanthin productivity was influenced by temperature, salinity, and the addition of urea. Nutrient enrichment by phosphorus did not enhance cell density and fucoxanthin productivity, while urea addition was found to stimulate both. We conclude that POME wastewater, supplemented with urea, can be considered as the potential medium for P. tricornutum to replace commercial nutrients while producing high amounts of fucoxanthin.