Heavy metals in the aquatic environment is a serious concern in the living organisms because they are assimilated and concentrated by organisms [1,2]. Divalent nickel is a commonly occurring toxic metal in natural ecosystems due to the effluents of refineries electroplating, casting industries storage batteries and nickel plating plants [3]. Acute Ni (II) poisoning causes dizziness, headache, nausea, cyanosis and DNA damage [2]. Though high toxicity has been observed for Ni(II), Ni0 is only slightly toxic [4]. Various methods have been proposed for the treatment of wastewaters containing Ni(II). TiO2 is as a important semiconductor in the area of wastewater treatment that is extensively used because of non-toxicity, low cost and chemically stable. Producing the electron–hole pairs are separated between the valance and conduction bands, on the surface of the catalyst and become involved in redox reactions. Any metal ions having a reduction potential less negative than conduction band would potentially be reduced by photogenerated electrons by photocatalyst. A cylindrical photo-sono reactor made of glossy stainless steel with total capacity of 1.25 L was used. The light source was a 250 W mercury lamp with the maximum emission of 365 nm. The lamp was located centrally and directly irradiated the aqueous solution around. In this work for the first time, Ni(II) photocatalytic reduction process was performed with very low amounts of nano TiO2 particles (less than 45 mg/L), as well as process modeling and optimization via RSM. Moreover, to the best of our knowledge, the influence of media temperature, has not been reported for this process so far. Accordingly, this parameter as well as solution pH, TiO2 dosage and reaction time are considered and the corresponding mathematical expression is developed to model the obtained reduction efficiency (RE). Based on the model, the best operating conditions are estimated and validated with confirmatory experiments. Under the best f