Benign encapsulation of living cells within stable, permselective materials holds exciting prospects for implantable autonomous therapeutics, but is challenged by the demand by such applications for materials bearing an optimal combination of microstructure, stability, and functionality. Here, we look to harness so-called Lys–Sil sols composed of stable and size-tunable silica nanoparticles in aqueous solutions of the basic amino acid l-Lysine for encapsulation of living mammalian cells. We highlight the benign and tunable solution conditions (i.e., particle size, pH, low concentration of oligomeric silicate species) of Lys–Sil sols, and demonstrate the remarkably robust particle stability in solutions ranging in complexity from purified water to cell growth media. Mammalian cells are encapsulated by dispersion in growth media containing Lys–Sil nanoparticles, the assembly of which is triggered by titration with di-lysine. We study the encapsulation of human umbilical vein endothelial cells (HUVEC), chosen as a sensitive representative mammalian cell line. Laser scanning confocal microscopy (LSCM) of the encapsulated cells and nuclear magnetic resonance (NMR) spectra of the growth media in contact with them are employed for complementary assessment of cell viability. Results suggest that the physiologically relevant conditions of the Lys–Sil sol promote the sustained viability of the encapsulated mammalian cells, and further underscore the potentially broader applicability of these sols for other benign materials syntheses.