The aim of this study was to investigate the molecular mechanism behind androgen-induced sex reversal and growth increase in Nile tilapia. Three-day-old mixed-sex tilapia juveniles were treated with differential dose (0, 5, 10, 20, 30 mg/kg diet) and duration (0, 15, 30, 45, 60 days) regimes of 17α-methyltestosterone. Treatment regimes 10, 20, 30 mg/kg-30, 45, 60 days showed ~95% males, while 0 mg/kg-0 days (control) showed ~50% males (P < 0.01). Next, tilapia was cultured for 6 months in cistern and pond culture systems with 17α-methyltestosterone-treated diet (10 mg/kg) for three different durations: 0 days (control), 30 days (30-day-treated), and 180 days (throughout-treated). Fish in pond culture showed significantly higher (P < 0.05) final weight compared with tilapia in cistern culture (235.76, 156.82 g, respectively). Both 30-day-treated and throughout-treated fish showed significantly higher (P < 0.05) final weight, length, daily weight gain, specific growth rate, and muscle protein content compared with control fish. The androgen receptor β mRNA and protein expression levels in both 30-day-treated and throughout-treated fish were significantly higher (~twofolds, P < 0.05) compared with hormone-untreated control males. However, there was not much difference for all these parameters among the two hormone-treated groups. This higher growth probably results from an androgen-induced increased ‘androgen-androgen receptor’ mediated anabolic pathway. Serum testosterone concentration of 30-day-treated fish after 6 months was similar to that of control males (0.9 ng/ml). Moreover, culture of 17α-methyltestosterone-treated monosex tilapia was found beneficial than hormone-untreated mixed-sex tilapia culture for maintenance of natural fish diversity in indigenous water bodies.