Nanotoxicity studies associated with various nanoparticles (NPs) have attracted intense research interest due to the broader applications of nanoparticles in our daily lives. The exposure of nanoparticles can lead to hypersecretion and accumulation of airway mucus which are closely associated with many respiratory diseases. Titanium dioxide (TiO), one of the PM10 components, is a major NP that is widely utilized in many commercial products. Our previous study established the connection between induced airway mucus secretion and TiO NPs. However, the countermeasure to reduce the harmful effects of TiO NPs, especially airway mucus secretion, remains unexplored. One of the potential candidates to reduce airway mucus secretion is cerium oxide (CeO) NPs. It has been reported that CeO NPs can protect cells by diminishing ROS and inflammatory responses. Herein, our study shows that CeO NPs are able to reduce cytosolic Ca changes and mitochondrial damage caused by TiO NPs. Our results provide the evidence that hypersecretion of mucus and apoptosis progression induced by TiO NPs can be attenuated by CeO NPs. This study highlights the potential capacity of CeO NPs as a supplementary material for TiO NPs applications in the future.