His appeal came after unions last week said hundreds of workers had been fired from a factory making sportswear for US giant Nike after a series of pay protests.
Cambodian workers have repeatedly demonstrated against low wages and tough conditions in the multibillion-dollar textile industry, which produces goods for top western brands.
Currently workers can earn around $110 a month with overtime.
Hun Sen said repeated protests may imperil the country's lucrative garment industry by persuading firms to relocate to Myanmar, Laos and India where labour is cheaper.
"If the investors move out, it will be a big disaster for our country," Hun Sen said in a speech broadcast on national radio.
"It is easy for garment and footwear factories to flee the country," he said, warning workers to be "cautious over high pay demands".
The premier said some $480 million was paid to workers across the country each month.
The textile industry, which employs about 650,000 people and produces clothes for top western brands, is a key source of foreign income for the country.
Hundreds of workers on Wednesday briefly blocked the road outside a factory in the capital Phnom Penh making clothes for Swedish clothes firm H&M protesting over healthcare payment, according to an AFP photographer.
The incident comes after 10 workers were injured when police broke up a June 3 demonstration at a factory in the southern province of Kampong Speu making goods for Nike.
Sixteen garment workers and union representatives have been charged with inciting violence and damaging property during the protest, judge Chhim Rithy, from Kampong Speu provincial court, told AFP.
Eight of the activists are being held in detention, the judge added.
A week earlier riot police allegedly used stun batons against the strikers.
Protesters said a pregnant woman suffered a miscarriage in that crackdown, and have accused the security personnel of using excessive force to quell the rallies.
Unionists rejected Hun Sen's comments.
"He (Hun Sen) does not know the hardship the workers are facing," said Chea Mony, leader of the Free Trade Union.
"Generally, the factory owners do not respect the laws or workers' rights."