The route will operate from December 18 to March 1 three times a week.
The carrier launched its Canton Route strategy this week, aiming to link Australia and Europe via Guangzhou.
CSN wants the Chinese hub to compete with the likes of Singapore, Hong Kong and Bangkok, as well as and emerging hubs Dubai, Doha and Abu Dhabi.
Cairns Airport CEO, Kevin Brown, said the new route followed several years of CSN successfully operating Chinese New Year charter flights into Cairns from Guangzhou.
“Cairns Airport has worked closely with China Southern over several years to secure a direct service from Guangzhou,” Brown said.
“The announcement of three flights per week into Cairns over two and a half months significantly extends China Southern’s previous Chinese New Year services and further demonstrates the airline’s confidence in our region.”
Cairns becomes the airline’s fifth Australian destination after Sydney, Melbourne, Brisbane and Perth.
The new service will be triangulated operating Guangzhou–Brisbane–Cairns–Guangzhou.
Brown said the airport would continue to press for a permanent direct service.
China Eastern, last month, announced a direct Shanghai–Cairns service three times a week from October.