A bombing at Cairo's largest Coptic cathedral killed at least 25 people and wounded 49, many of them women and children attending Sunday mass, in the deadliest attack on Egypt's Christian minority in years.

The attack comes as Egyptian President Abdel Fattah al-Sisi battles against an militant insurgency in Northern Sinai, led by the Egyptian branch of Islamic State (IS).

The militant group has also carried out deadly attacks in Cairo and has urged its supporters to launch attacks around the world in recent weeks as it goes on the defensive in its Iraqi and Syrian strongholds.

There was no immediate claim of responsibility.

The explosion took place in a chapel adjoining the main hall of St Mark's Cathedral, the largest in the metropolis of 20 million, where security is normally tight. The chapel floor and pews were covered with debris, dust and sticky patches of blood.

“As soon as the priest called us to prepare for prayer, the explosion happened,” Emad Shoukry, who was inside when the blast took place, told Reuters. “The explosion shook the place... The dust covered the hall and I was looking for the door, although I couldn't see anything... I managed to leave in the middle of screams and there were a lot of people thrown on the ground.”

Security sources told Reuters at least six children were among the dead, with the blast detonating on the side of the church normally used by women.

They said the explosion was caused by a device containing at least 12 kg (26 pounds) of TNT. Police were investigating claims by witnesses that the bomb was concealed in the handbag of a woman who had placed it on the floor of the church and left.

Police and armoured vehicles rushed to the area, as dozens of protesters gathered outside the compound demanding revenge. Scuffles broke out with police.

A woman sitting near the cathedral in traditional long robes shouted “kill them, kill the terrorists, what are you waiting for?.... Why are you leaving them to bomb our homes? Egyptian blood is cheap!”

Though Egypt's Coptic Christians have traditionally been supporters of the government, angry crowds turned their ire against Sisi, saying his government had failed to protect them.

“As long as Egyptian blood is cheap, down, down with any president...” they chanted.

Others chanted “the people demand the fall of the regime”, the rallying cry of the 2011 uprising that helped end Hosni Mubarak's 30-year rule.

Sisi's office condemned the attack as an act of terrorism and declared three days of national mourning. Al Azhar, Egypt's main Islamic centre of learning, also denounced the attacks.

Orthodox Copts, who comprise about 10 percent of Egypt's 90 million people, are the Middle East's biggest Christian community.

Copts face regular attack by Muslim neighbours, who burn their homes and churches in poor rural areas, usually in anger over an inter-faith romance or the construction of church.

The last major attack on a church took place as worshippers left a new year's service in Alexandria weeks before the start of the 2011 uprising. At least 21 people were killed.

Egypt's Christian community has felt increasingly insecure since IS spread through Iraq and Syria in 2014, ruthlessly targeting religious minorities. In 2015, 21 Egyptian Christians working in Libya were killed by IS.

Coptic Pope Tawadros II cut short a visit to Greece after learning of the attack. Coptic officials said they would not allow the bombing to create sectarian differences.

“We will not allow the terrorist to threaten our national unity with Muslims,” Hani Bakhoum, undersecretary of the Coptic Catholic Patriarchate told Egyptian state television.