The performance of cement-based materials depends on the characteristics of solid particles at the nano-scale or nanometer porosities in the interfacial transition zone between cement particles and aggregate. Heat significantly affects the properties of these particles and the connection between them. Accordingly, the present study seeks to investigate the effect of nano-silica on the strength parameters of sand–cement mortar at high temperatures. In this regard, the sand–cement mortar was prepared by replacing 5, 10, and 15 percent of cement with nano-silica. The specimens were subjected to temperatures of 25, 100, 200, 400, 600, and 800 °C after curing at the ages of 3, 28, and 90 days. The effect of high temperatures on the physical and mechanical properties of sand–cement mortar was analyzed using macro-structural tests of compressive strength, loss in weight, and water absorption, and microstructural tests of X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results revealed that the macro-structural behavior of sand–cement mortar highly depends on the microstructure and changes in cement nanostructures during heat treatment. Primary portlandite and C–S–H nanostructure were destroyed at 600 °C, and alite, belite, and β-wollastonite were formed at 800 °C. Adding nano-silica improved the strength properties of sand–cement mortar against heat, so the compressive strength of 28-day specimens containing 15% nano-silica increased from 13.9 to 19.2 MPa at a temperature of 800 °C.