The over-expression of foreign proteins imposes metabolic burden on host strains that may lead to reduced cell growth and even yield of target protein. We investigated dependency of co-expression effects of stress-induced non-specific DNA-binding protein, Dps, on cell growth and foreign protein expression according to solubility in Escherichia coli. Dps co-expression showed clear distinct effects according to solubility of target proteins. Under co-expression of recombinant Dps, cell growth for the strain expressing baculoviral polyhedrin (Polh)-green fluorescent protein (GFP) fusion protein or human interleukin-2 (hIL-2) that were expressed as insoluble inclusion body had tendency to decline slightly compared to each Dps non-expressing strain. However, cell growth for the strain expressing soluble GFP or mussel adhesive protein type 5 (Mgfp-5) was somewhat increased. While Dps co-expression had somewhat negative effects on expression of soluble protein, it showed huge impacts on product yield of insoluble proteins (1.6–1.8-fold for Polh-GFP and 4–5-fold for hIL-2). Therefore, it was obvious that co-expression of Dps has different effects on foreign protein production according to solubility. Proteomic analyses revealed that Dps co-expression induced significantly different global patterns through interaction with target foreign protein according to target solubility. These global pattern alterations might be favorable for production of insoluble foreign proteins indirectly.