The shop operated by China Duty Free Group (CDFG) is under construction and expected to open in December, the Phnom Penh Post reported on Wednesday, citing general manager John Zhao.
Another store in downtown Phnom Penh will be launched next year, he said.
The combined investment cost of the two shops is US$35 million (1.12 billion baht), he added.
Cambodia has duty free shops at airports in Phnom Penh and Siem Reap.
The shop in downtown Siem Reap is the first expansion of the Chinese firm outside China.
The company decided to land its offshore expansion in Cambodia due to its booming tourism industry, Mr Zhao was quoted as saying.
About 2.2 million foreign tourists visited Cambodia during the first six months of this year, a 5% increase over the same period last year, the Xinhua news agency said, citing a report of the Cambodian Tourism Ministry released on Wednesday.
Vietnam topped the visitors list followed by China.
Home to Angkor Wat, Siem Reap is the most popular tourist stop in Cambodia.