In the present study, the biochemical responses and antioxidant enzymes activity of the Dunaliella salina, a green microalga, to the interaction of silver nanoparticles (AgNPs) and salicylic acid (SA) were investigated. Algal suspensions in the phase of logarithmic growth were subjected to the concentrations of 0, 5, 15, and 25 pM AgNPs with or without 1 mM SA. AgNPs level of 25 pM declined cell division but highly accumulated levels of chlorophyll, β-carotene, proteins, free amino acid, carbohydrates, and hydrogen peroxide, which was associated with enhanced the activity of proteolysis, lipid peroxidation, and antioxidant enzymes. SA-treated cells at 25 pM AgNPs improved cell growth but declined the activities of antioxidant enzymes and proteolytic along with a lower accumulation of metabolites except β-carotene relative to untreated controls. These results suggest that AgNPs treatment induce oxidative stress in D. salina cells, which tolerated by alga through the metabolic modifications and accumulating β-carotene, while SA induces AgNPs tolerance by the mechanisms that direct carbon flux to growth and β-carotene biosynthesis rather than the antioxidant enzymes or osmoprotectant metabolites.