The health department in Guangdong province, where Shenzhen is located, announced on Saturday that the bus driver died after his lung, heart and liver functions deteriorated.
"So far, 120 people who have had close contact with him have not presented abnormal symptoms," it said in a statement.
Chinese and Hong Kong authorities have been working closely together since December 21 after live poultry supplies were suspended to the glitzy financial hub following the discovery of infected birds.
A spokesman for the Hong Kong health department said in a statement authorities would heighten their vigilance "and continue to maintain stringent port health measures in connection with this development".
China is considered one of the nations most at risk of bird flu epidemics because it has the world's biggest poultry population and many chickens in rural areas are kept close to humans.
In the last reported human case in China, a young pregnant woman died of bird flu in June 2010 in the central province of Hubei.
The bus driver's death brought to 27 the number of people who have died in China since 2003, out of 41 reported human cases.
Authorities in Hong Kong have raised the bird flu alert level to "serious" since they discovered infected chickens, resulting in major disruptions to poultry supplies over the busy Christmas period.
The avian influenza virus has killed more than 330 people around the world, with Indonesia the worst-hit country. Most human infections are the result of direct contact with infected birds.
Scientists fear H5N1 could mutate into a form readily transmissible between humans, with the potential to cause millions of deaths.
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