The continuous release of manufactured nanomaterials (MNMs) to environments raised concerns on their combined toxicological risks with co-existing contaminants, since MNMs might severely alter the environmental behavior and fate of the contaminants. In this study, the combined toxicity of nano-sized titanium dioxide (nTiO) and cadmium (Cd) to the green alga Scenedesmus obliquus and the underlying physicochemical mechanisms were investigated for the first time at different concentration ratios of Cd to nTiO to closely mimic the realistic environment scenarios where the concentration ratios of nTiO to other contaminants are constantly changing. Our results suggested that under the co-exposure to different concentration ratios of Cd to nTiO, the co-exposure contaminants exhibited three different combined toxicity modes (antagonistic, partially additive, and synergistic). Specifically, antagonistic combined toxicity was observed under co-exposure to a low concentration ratio of nTiO to Cd as the absorption by nTiO decreased the bioavailability of Cd. However, the partially additive and synergistic combined toxicity occurred when the proportion of nTiO in the co-exposure system was relatively high, which would mechanically and/or oxidatively damage the alga cell structures. Even worse, as a carrier of Cd, nTiO enhanced the amount of Cd entering cells, which significantly enhanced the toxicity of Cd to algae. Overall, we demonstrated that concentration ratios of nTiO to Cd play an important role in determining the combined toxicity mode, which would provide a novel reference to environmental and health risk assessment of co-exposure to conventional pollutants and MNMs.