The presence of nanoparticle fractions (<100 nm, NPs) in the food additive TiO2 (E171) rises concerns about its potential harmful impact on human health. The knowledge about the interaction of TiO2 NPs with food components is limited to proteins or polyphenols. The present paper is the first to report on interactions between TiO2 NPs and high molecular pectins that form gels in boluses and are remain nearly intact during digestion until they reach the colon. Direct interactions were studied using Fourier Transform Infrared Spectroscopy while indirect ones were monitored by measuring the “absorption” of TiO2 using a 0.2 microfiltration membrane, during in vitro digestion in a model of the gastro-intestinal tract. The FT-IR spectra registered for pectin-TiO2 NPs solutions confirmed changes in band intensities at 1020, 1100, 1610, and 1740 cm−1, suggesting interactions taking place mainly via the COO– groups. Furthermore, the I(1020)/I(1100) ratio was decreased (C-O stretching vibrations), suggesting partial blocking of the skeletal vibrations caused by interactions between pectin and TiO2. The modelled in vitro digestions confirmed that the “availability” of Ti was reduced when TiO2 NPs were combined with pectin, as compared to TiO2 NPs “digested” alone.