The 25-year-old fly-half for the Harlequins has not yet played in the competition because of a calf ailment.
Half of Scrum Alex Mitchell is also eligible following his absence from the Scotland loss at Murrayfield due to a knee injury.
At 16:45 GMT on Saturday, England plays Ireland, the team chasing a grand slam.
Before the opening match against Italy at the beginning of February, Smith suffered a calf injury during training, ending his chances of playing a key role in the Six Nations.
For England’s three matches thus far, George Ford of Sale has worn the number 10 shirt in his absence, with Fin Smith of Northampton making his apperance.
