The England international last featured in his side's 2-0 victory over Tottenham Hotspur on 11 February and has been sidelined since then with a foot injury. Liverpool manager Jurgen Klopp was hopeful that the midfielder will return to the pitch against their local rivals.
Henderson was a part of Liverpool's young group that travelled to Tenerife during the last international break. He trained with other players and was expected to make himself available for the team selection on Saturday.
According to the Liverpool Echo, the former Sunderland man will miss the clash against Ronald Koeman's side after he missed the training on Thursday. He has been out of action for five weeks and will continue to be on the sidelines as he looks to recover from the foot injury.
The Reds star player's absence will be a massive blow for Klopp as Liverpool are already without the services of Adam Lallana. The ex-Southampton star picked up a thigh injury while on international duty with England and is expected to out of action for a month.
With Lallana and Henderson out of action, the former Borussia Dortmund manager is left with Georginio Wijnaldum, Emre Can and Lucas Leiva as the three recognised midfielders in the squad.
It should be seen whether Klopp will start Lucas against Everton or allow Philippe Coutinho to drop in the midfield. Should Liverpool manager decide to go with the latter, then Divock Origi is likely to lead the Reds' attack against Everton.
Meanwhile, Daniel Sturridge has returned to training on Thursday after recovering from a hip injury. The injury-plagued England striker worked with Liverpool's rehab squad and did not train with the main squad.
It is likely that the former Chelsea man be on the substitutes bench during the derby clash. The last time Liverpool and Everton faced each other saw the Reds seal a narrow 1-0 win after Sadio Mane tapped in the late winner.