The FC Istiklol 2016 season is Istiklol's eighth Tajik League season. They are the current defending Champions in the Tajik League, Tajik Cup and Tajik Supercup having completed a Domestic Treble during the 2015 season. They will also participate in the AFC Cup for the second time, entering at the group stage.
On 10 July 2016, Istiklol fired their entire coaching staff, including manager Mubin Ergashev, appointing Serbian Nikola Lazarevic as his replacement on 13 July 2016. On 31 October 2016, days after winning their fifth Tajik League title, Istiklol appointed Mukhsin Mukhamadiev as their new manager for the 2017 season.
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|- |colspan="14"|Players away from Istiklol on loan: |- |colspan="14"|Players who left Istiklol during the season: