For this study, we used titanium dioxide (TiO2), produced using nanotechnology. To show its superiority with respect to talc, we completed an in vitro study comparing the pro-inflammatory response of both agents towards malignant and benign mesothelial cells; researching the possible apoptosis induction and possible inhibition of angiogenesis for both agents. We took a culture of cell lines derived from human mesothelioma, originating from human biphasic mesothelioma and human bronchial adenocarcinoma. The cells were cocultured with different doses of talc and TiO2 nanoparticles. The levels of different inflammatory mediators were analyzed for each culture supernatant sample. The apoptosis rate was analyzed using caspase-3 expression. The endostatin levels were determined for the angiostasis study using the ELISA technique. We observed that the viability of the benign mesothelial cells is much lower after using TiO2. In the case of malignant mesothelial cells, the same effect was observed with a high dose of TiO2. In adenocarcinoma of the lung, the viability of these cells exposed to talc was distinctly lower than that which was observed in the benign cell line. IL-8 production was much higher in neoplastic mesothelial cells than in benign cells and increased following a dose-dependent pattern with talc, while it decreased with TiO2. According to these results, we can see that talc is superior to TiO2 in its ability to produce mediators which favor pleurodesis for the control of malignant pleural effusions.