One of the key shortcomings in the field of nanotechnology risk assessment is the lack of techniques capable of source tracing of nanoparticles (NPs). Silica is the most-produced engineered nanomaterial and also widely present in the natural environment in diverse forms. Here we show that inherent isotopic fingerprints offer a feasible approach to distinguish the sources of silica nanoparticles (SiO
2
NPs). We find that engineered SiO
2
NPs have distinct Si–O two-dimensional (2D) isotopic fingerprints from naturally occurring SiO
2
NPs, due probably to the Si and O isotope fractionation and use of isotopically different materials during the manufacturing process of engineered SiO
2
NPs. A machine learning model is developed to classify the engineered and natural SiO
2
NPs with a discrimination accuracy of 93.3%. Furthermore, the Si–O isotopic fingerprints are even able to partly identify the synthetic methods and manufacturers of engineered SiO
2
NPs.