The Israeli military said it was opening an additional route for 48 hours that Palestinians could use to leave Gaza City as it stepped up efforts on Wednesday to empty the city of civilians and confront thousands of Hamas combatants.

Hundreds of thousands of people are sheltering in the city and many are reluctant to follow Israel's orders to move south because of dangers along the way, dire conditions, a lack of food in the southern area and fear of permanent displacement.

"Even if we want to leave Gaza City, is there any guarantee we would be able to come back? Will the war ever end? That's why I prefer to die here, in Sabra, my neighbourhood," Ahmed, a schoolteacher, said by phone.

In leaflets dropped over Gaza City, the military said Palestinians could use the newly reopened Salahudin Road to escape towards the south and that they had until lunchtime on Friday to do so.

At least 63 people were killed by Israeli strikes and gunfire across the Gaza Strip on Wednesday, with most of the casualties in Gaza City, local health authorities said.

Among those killed were 13 people, including local TV journalist Mohammad Alaa Al-Sawalhi, who medics said were complying with the order to leave Gaza City.

Another five people were killed and dozens wounded by Israeli gunfire near an aid site in Rafah, local health officials said. The Israeli military said troops had fired warning shots to remove an "immediate threat."

The Hamas-run government's Ministry of Health said an Israeli drone dropped grenades on one floor of the Rantissi children's hospital on Wednesday. No casualties were reported but the ministry said some 40 families took their children away.

"This hospital is the only specialist facility for children with cancer, kidney failure and other life-threatening conditions – but even these gravely ill children are not spared from relentless bombardment," said Fikr Shalltoot, Gaza director at the UK-based charity Medical Aid for Palestinians.

Israel estimates about 400,000 people, or 40 percent of those who were in Gaza City on August 10 – when it announced plans to take control – have already fled. The Gaza media office says 190,000 have headed south and 350,000 have moved to central and western areas of the city.

A day after Israel announced the launch of its ground offensive to seize control of Gaza's main urban centre, tanks had moved short distances towards the city's central and western areas from three directions, but no major advance was reported.

An Israeli official said military operations were focused on getting civilians to head south and that fighting would intensify over the next month or two.

The official said Israel expected around 100,000 civilians to remain in the city, which would take months to capture, and said the operation could be suspended if a ceasefire was reached with the Hamas militant group.

The prospects of a ceasefire appear remote after Israel attacked Hamas political leaders in Doha last week, infuriating Qatar, a co-mediator in ceasefire talks.

Defying global criticism of the attack, including a rebuke by Israel's stalwart ally, the United States, Prime Minister Benjamin Netanyahu has said Israel would strike Hamas leaders anywhere. (Reuters)