The accident happened on the M4 westbound carriageway near Newport in South Wales, prompting a huge emergency services response on the afternoon of Saturday 5 February.
Four-year-old Gracie-Ann Wheaton, from Tredegar, died in hospital in the early hours the following day, while the three-year-old boy remained critically ill in hospital.
A GoFundMe page said the little boy had also died.
The car was travelling on the motorway’s westbound carriageway when it was hit by a van.
The “wonderful” youngster, who has been described as having a “kind soul”, cannot be named for legal reasons.
A family member told the PA news agency: “Unfortunately, after a week of fighting, he has passed away.
“He was wonderful, creative and a kind soul. Turned the grey skies blue.”
The GoFundMe page set up in the aftermath of the crash has raised almost £10,000.
The driver of the Ford Transit, 41-year-old Martin Newman, of Croeserw, appeared at Newport Magistrates’ Court on Monday charged with causing death by dangerous driving and two offences of causing serious injury by dangerous driving in relation to the accident.
He has been remanded into custody pending a hearing at Newport Crown Court on 21 February.
Anyone with dashcam footage of the collision, or any information that could help the investigation, is asked to call Gwent Police on 101 and quote 2200041245.
via IRN/Sky News for GTFM