The impact of both boron (H₃BO₃) and cadmium (CdCl₂) on some physiological and histological parameters was assessed on the Nile tilapia (Oreochromis niloticus). Six treatments including a control were used, with concentrations of 29mg/ L and 72.5mg/ L for boric acid, a concentration of 6.25mg/ L for cadmium, and combinations of (B 29mg/ L + Cd 6.25mg/ L) and (B 72.5mg/ L + Cd 6.25mg/ L). The chronic influence of boron and cadmium on heat shock protein (Hsp70) in musculature, liver function, antioxidant enzymes, and histopathology of liver and gills were studied. The relative expression of HSP70 in B₂₉, B_72.5, B₂₉+Cd, B_72.5+Cd, and Cd was P= <0.0001, P= 0.0018, P= 0.0198, P= 0.4573, and P= 0.9814, respectively, in comparison with the control group. ALT, AST, and ALP enzymes activities demonstrated significant differences between treatments. Liver antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities showed significant differences between treatments. Histopathological investigation of fish liver and gills in treated groups revealed severe hemorrhage and congestion of sinusoids for the liver. Moreover, the investigation showed severe lamellar lifting and lymphatic infiltration in the gills. In cadmium-treated groups, the liver showed moderate congestion and lymphatic infiltration, and the gills showed moderate raising of lamellae epithelial and mild lamellar aneurysm.