Yang Hengjun, a blogger and former Chinese diplomat, has not been heard from since flying from New York to Guangzhou on Saturday, a friend said.
Sydney academic Feng Chongyi said he feared that Mr Yang had been detained by Chinese authorities.
A Chinese foreign ministry spokeswoman said she was "not aware" of the case.
Mr Yang is believed to have been travelling with his wife, Chinese national Yuan Rui Juan, and young stepson.
A social media post by Ms Yuan appeared to show that she was in Beijing, Australian media reported.
It is believed that she was interviewed there by Chinese officials after first travelling to Shanghai to leave her son with relatives, the BBC's Stephen McDonell in Beijing reports.
'We've been trying to contact him'
Mr Yang, an Australian citizen who now lives in the US, has a sizeable following online and has been critical of China's Communist Party.
He was briefly unreachable on a trip to China in 2011 - prompting fears he was missing - but later attributed the episode to a "misunderstanding".
Associate Prof Feng, an academic at University of Technology Sydney, said he had warned Mr Yang recently against travelling to China, but that Mr Yang had replied that he considered himself to be safe.
"His friends, family, myself - we have been trying to contact him and her these past four days and we all [failed]," Associate Prof Feng told the BBC.
Another friend, Australian journalist John Garnaut, told the Sydney Morning Herald: "Let's hope he reappears today and we can all agree there's just been a misunderstanding."
In response to a query about Mr Yang, Australia's Department of Foreign Affairs and Trade said it was "seeking information about an Australian citizen who has been reported missing in China".
Chinese foreign ministry spokeswoman Hua Chunying said she was not aware of the case but would ask relevant departments for information.
Correspondents say this follows a similar pattern to the cases of two Canadian citizens, Michael Kovrig and Michael Spavor, who were detained in China in recent weeks.
In both cases, the foreign ministry initially said it had no knowledge of them being held, then confirmed they were in the hands of state security a few days later.
Australia has previously expressed "concern" about the arrests of the Canadians.
China has denied the detention of the two men is tied to Canada's arrest of a senior Huawei official, Meng Wanzhou, but many analysts believe it is a tit-for-tat action.
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