Titanium dioxide (TiO2) nanomaterials (NMs) have been widely used to develop commercial products such as sunscreen cosmetics because of their unique optical properties to provide complete protection from ultraviolet (UV) light. The most dangerous type of UV radiation is UVA, which comprises nearly 97% of the UV radiation that reaches the Earth. This type of radiation is also the major cause of skin damage. As the most beneficial content of sunscreen cosmetics, TiO2 NMs exhibit immense capability to protect the human skin from UVA exposure through their scattering and reflecting physical properties. Therefore, investigating the factors involved in using TiO2 NMs in cosmetics is necessary. In this study, various human oral and lung cell lines were selected to evaluate the cytotoxicity of treatment using different sizes and shapes of TiO2 NMs, including spheres (AFDC and AFDC300) and rods (M212 and cNRs). The morphology, size, and crystalline phase of the selected TiO2 NMs were studied to characterize each physical property. Based on cell viability and endocytic behavior results, treatment with all the selected TiO2 NMs were nearly non-toxic to the oral cell lines. However, high cytotoxicity was obviously observed in lung cells with M212 and AFDC treatments at 50 μg mL-1, which was larger by approximately 20% than with ADC300 and cNRs treatments because the smaller the TiO2 NMs, the larger their specific surface area. This condition resulted in the progress of apoptosis from the considerable aggregation of TiO2 NMs in the cytoplasm. Moreover, compared with those of TiO2 NMs with a similar structure (e.g., cNRs) and size (e.g., M212), the cellular uptake of AFDC was evidently low, which resulted in the approximated non-toxicity. Moreover, the similar sizes and different shapes of AFDC and cNRs were considered to treat lung cells to investigate further the influence of morphology on the cell cycle and the apoptosis effect. Consequently, AFDC and cNRs could inhibit the growth of lung cells and allow a considerable proportion of the cells to remain in the G1/G0 phase. Furthermore, a high-dose treatment would directly induce the apoptosis pathway, whereas a low-dose treatment might decrease cell regeneration.