The objective of the research was to evaluate the effect of disinfectants on surface hardness and flexural strength of denture base resins added with nanofiller and crosslinking agent. Four different weight percentages of nanosilica filler particles and crosslinking agents were incorporated in heat cure acrylic resin. Acrylic discs and rectangular blocks were fabricated. They were stored in distilled water for 48 hours. Specimens were then grouped and each group was treated with one of the media: gluteraldehyde, chlorhexidine gluconate and sodium hypochlorite for ten minutes. After immersion, the specimens were kept in water. The Vickers hardness and flexural strength was tested at different time intervals. Acrylic resin specimens reinforced with 1 mass % nanosilica filler particles exhibited higher surface hardness and flexural strength. Addition of 1 mass % crosslinking agent exhibited higher surface hardness and 1 and 2 mass % crosslinking agent exhibited higher flexural strength. Surface hardness reduced with all the disinfectant media. The least damage was caused by sodium hypochlorite. The least damage on flexural strength was caused by gluteraldehyde.