The statement said the resistant strain of influenza A (H1N1) was detected during routine tests of its sensitivity to anti-virals.
"This is the first time Tamiflu resistance in HSI virus (has been) found in Hong Kong," a spokesman said.
The case came as the Japanese health ministry said doctors had detected the second case worldwide of a patient resistant to Tamiflu, widely used to treat the illness.
In the Hong Kong case the resistant virus was isolated from a specimen taken from a 16-year-old girl who arrived in the southern Chinese city from San Francisco last month.
She was admitted to hospital and opted not to take Tamiflu, the spokesman said, but was discharged after a week.
The strain is not resistant to the other anti-viral drug, Relenza, the health department said.
A spokeswoman for Swiss pharmaceuticals giant Roche, which makes Tamiflu, said the company had been informed of the case and called it "normal."
"It is absolutely normal," she said, adding that "0.4 percent of adults develop resistance" to Tamiflu.
Last month, authorities ordered all primary schools in Hong Kong to be closed for two weeks after the first cluster of local swine flu cases was found.
When Hong Kong discovered its first case, in early May, health authorities quarantined around 300 guests and staff at a hotel where the carrier, a Mexican, had briefly stayed.
Hong Kong is particularly nervous about infectious diseases following the outbreak of the SARS virus in 2003, which killed 300 people here and a further 500 around the world.
The latest numbers from the World Health Organization, released on Wednesday, showed 77,201 reported swine flu cases, with 332 deaths.
In Japan, the health ministry said doctors in Osaka prefecture had identified a woman who was resistant to Tamiflu -- the second such case, after one found in Denmark.
The Japanese woman had since been treated with Relenza and was recovering, Kyodo news agency reported Thursday, citing the health ministry.
In China, furious relatives of a woman who died while being treated for suspected swine flu stoned an ambulance in a rampage at a hospital in the eastern city of Hangzhou, state news agency Xinhua reported.
Initial reports stoked fears she might be the first person in China to die from swine flu, but police said on Friday that an autopsy had shown she died of an electric shock.
Xinhua reported that the woman had shown no symptoms of swine flu at the time of death, barring an occasional cough.