Biofloc based aquaculture is important in waste recycling in intensive aquaculture and is a promising avenue for inland saline aquaculture. In the present study, growth, biochemical and carcass quality of red tilapia reared in inland saline waters of different salinities based on biofloc technology was estimated during 90 days culture period. Fifteen experimental tanks (500 L each) were filled with inland saline ground water to represent 5 biofloc treatments with variable salinities such as T1 (5 ppt), T2 (10 ppt), T3 (15 ppt), T4 (20 ppt) and control (0 ppt) in triplicates. Red tilapia fry with average body weight of 13.78 ± 0.62 g were stocked at the rate of 150 no.m ‐3 in each biofloc unit. The units maintained at higher salinity (20 ppt) obtained significantly better (P < 0.05) growth performances in terms of percentage weight gain (329.89 ± 13.41), specific growth rate (1.65 ± 0.05), protein efficiency ratio (1.18 ± 0.07) and feed conversion ratio (0.93 ± 0.06). Biochemical properties such as serum glucose (118.49 ± 3.73 mg dL−1), serum total protein (4.23 ± 0.04 mg dL−1), total serum albumin (2.08 ± 0.03 mg dL−1), and total serum globulin (2.16 ± 0.04 mg dL−1) contents were the highest in T4 (20 ppt), whereas activities of enzymes, superoxide dismutase and catalase were the highest in control (0 ppt). Treatment T4 (20 ppt) had shown the highest survival rate (95.56 ± 1.28), carcass quality like firmness (121.45 ± 1.91), and whiteness (49.52 ± 0.79) and in addition, overall sensory attributes were also the highest in T4 (20 ppt). Consequently, the findings of the current investigation have shown that growth efficiency, survival, biochemical indices and carcass quality of red tilapia had improved when reared in higher salinity using inland saline groundwater.