The sliding friction between single silica microspheres was examined by applying friction force microscopy to probe the interaction between spherical silica particles glued to a tipless atomic force microscopy (AFM) cantilever and another particle glued to a glass slide. A three-dimensional model handling the complex contact geometry between spherical particles was established to compute friction and normal forces at the sliding interface from measured deflections of the AFM cantilever. Results obtained at different loads show a linear relationship between friction and normal force, with a friction coefficient of 0.4 between silica spheres. Friction in this system occurs at multi-asperity contacts. The results show that the macroscopic friction law of Amontons can be used to model the friction behavior of micrometer-sized granular matter. For plasma-treated silica particles, increased friction as well as wear could be observed during sliding.