Kasyanov was measured in reacting to the tumultuous events overtaking oil giant Yukos in the recent days, but his remarks are still being considered a rebuke for the investigators, who first arrested the Yukos chief and then seized almost half of the company's shares.
"I will withhold from any analysis, but I am deeply concerned," the prime minister said.
"The impounding of shares of stock-holding company whose shares are traded on the market is a new phenomenon, whose consequences are difficult to predict," Kasyanov said in televised remarks on Friday.
His comments underlined the deep divisions that the crackdown on Yukos has plunged the Kremlin in.
In publicly airing his concern, Kasyanov surely flouted President Vladimir Putin's instructions to members of his government not to speak publicly about Yukos and the imprisonment of its chief Mikhail Khodorkovsky.
The prime minister's remarks came a day after Putin was compelled to accept the resignation of his influential chief of staff Alexander Voloshin.
Voloshin is reported to have quit in protest over the arrest of Khodorkovsky.
Russian news-agency Interfax quoted Putin as telling Voloshin in a private meeting that he thought the resignation was a "mistake."
"I will withhold from any analysis, but I am deeply concerned"
Russian Prime Minister
Russian prosecutors meanwhile continued to come under fire for their handling of the Yukos affair.
Many viewed the crackdown on Yukos as political vendetta since Khodorkovsky funded opponents of Putin.
Analysts questioned the very legitimacy of the freezing of Yukos shares, though prosecutors said it was meant as collateral against the more than $ 1 billion that they accuse Yukos managers of misappropriating in the 1990s.
But several analysts noted the shares frozen were worth at least 10 times the alleged theft and the prosecutors broke laws by seizing shares of people never named in the government indictment.
Prosecutors tried to fix the oversight on Friday by unfreezing 4.5% of the impounded shares they said belonged to people who were not under investigation.