Photographs confirming his death and apparent torture were smuggled out of Syria by a forensic photographer.
Lawyers for the woman said the alleged crimes were "state terrorism".
Judge Eloy Velasco ruled that Spain has the jurisdiction to investigate the allegations against nine members of the Syrian security and intelligence forces - the first time such a decision has been made.
Because the deceased's sister, Amal Hag Hamdo Anfalis, is a Spanish national, and family members of those killed in international crimes can be considered victims, Judge Velasco ruled Spain could investigate the alleged crimes.
The photographs presented to the court of her brother, a truck driver named Abdul Hamdo, were part of a large tranche smuggled out of Damascus by a photographer codenamed "Caesar" in 2013.
His photos, which showed 6,786 people who died after detention, were verified as authentic by Human Rights Watch after months of investigation.
Judge Velasco asked that both "Caesar" and Amal Hag Hamdo Anfalis testify in the case in April.
The International Criminal Court has general jurisdiction on war crimes, although Syria is not a member state.
The United Nations, however, could grant the ICC jurisdiction by formally referring the case to the court.
But Russia, a veto-holding member of the UN Security Council, has blocked a previous attempt by UN member states to refer Syria to the ICC, as well as motion calling for an immediate end to hostilities.
French President Francois Hollande has suggested Russia could itself face war crimes charges over its actions in Syria.
Russia withdrew its signature from the Rome statute in November last year, but had never formally completed the process of signing up to the ICC.
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