The interactions of nanoparticles with human cells are of large interest in the context of nanomaterial safety. Here, we use live cell imaging and image-based fluorescence correlation methods to determine colocalization of 88 nm and 32 nm silica nanoparticles with endocytotic vesicles derived from the cytoplasmic membrane and lysosomes, as well as to quantify intracellular mobility of internalized particles, in contrast to particle number quantification by counting techniques. In our study, A549 cells are used as a model for human type II alveolar epithelial cells. We present data supporting endocytotic uptake of the particles and subsequent active transport to the perinuclear region. The presence of particles in lamellar bodies is proposed as a potential exocytosis route. Live cell imaging and image-based fluorescence correlation methods were used to quantify the intracellular mobility and interactions of 32 and 88 nm silica nanoparticles in A549 cells as model for human type II alveolar epithelial cells. Our data support uptake by endocytosis and active transport to the perinuclear region.