The Philippine Institute of Volcanology and Seismology (Phivolcs) registered the earthquake on Wednesday at 7.37 pm local time (11.37 GMT) at magnitude-6.3 at a depth of 15 km.
The quake was followed by some 246 aftershocks, including two tremors above magnitude-5, according to Phivolcs.
In Tulunam, North Cotabato province, a seven-year-old girl died in a house collapse due to the earthquake, the epicenter of which was located 22 km from the city.
In the nearby city of Kidapawan, a man died of a heart attack during the tremor, which had a magnitude of 6.4 at a depth of 14.1 km according to the US Geological Survey (USGS).
Another two-year-old girl died in a house collapse, and two people died due to a landslide in the city of Magsaysay, Davao del Sur province, according to Phivolcs.
In Magsaysay, most homes were "totally destroyed," said city hall spokesman Anthony Allada.
In General Santos, also in Davao del Sur, a shopping center caught fire after the earthquake, although an official casualty count has not been disclosed.
The Philippines sits on the so-called Pacific Ring of Fire, an area of great seismic and volcanic activity that is shaken by about 7,000 tremors a year, mostly moderate.
This year the country has suffered several earthquakes of over magnitude-5.
The deadliest occurred in the province of Pampanga last April, which left 16 dead, and another last July in Batanes on the northern tip of the country, leaving nine dead.
( With inputs from IANS )