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Desalination concentrate (DC) is a potential medium for microalgal cultivation since it contains an abundance of mineral salts. In this study, the feasibility of growing Chlorella vulgaris with DC was evaluated and the influence of DC concentration on the growth, biomass productivity, and biochemical composition was assessed. Media comprised of DC mixed with bold basal medium (BBM) in different concentrations were prepared for microalga cultivation. A sequential statistical methodology, comprising fractional factorial design and response surface methodology (RSM) was applied to enhance the biomass production. The growth of C. vulgaris was promoted with 75 % BBM + 25 % DC compared with the BBM control. C. vulgaris biomass production (0.59 g L−1) was observed with 75 % BBM + 25 % DC with optimal concentrations of sodium nitrate (0.09 g L−1), monobasic potassium phosphate (0.014 g L−1), and micronutrient solution (0.20 mL L−1). The gradual increase of DC had a strong effect on the biochemical composition of C. vulgaris. Carbohydrate fiber and protein contents were estimated to be 14.4 and 51.3 %, respectively, when the microalgae were cultivated in 75 % BBM + 25 % DC. The lipid content (12.5 %) of C. vulgaris cells was highest at the optimized BBM DC concentrations. When grown in the BBM control and optimized BBM + DC media, C. vulgaris produced lipids rich in polyunsaturated fatty acids (C18:3 ω3) and monounsaturated fatty acids (C18:1). These results indicated that DC is a feasible alternative for the mass cultivation of C. vulgaris.