"We would hope that as Japan examines its relationship with Iran, it would take into account, in any business transaction or any proposals that come along, the fact that Iran is not behaving in a responsible manner," Powell said in an interview with a group of Japanese reporters.
He noted that the International Atomic Energy Agency (IAEA) had found "serious deficiencies" in Iran's compliance with the nuclear Non-Proliferation Treaty and that Tehran was going back on promises it made to three European nations to halt all uranium enrichment activities.
"It seems clear to us that Iran is trying to develop a nuclear weapon and it is essentially saying to the international community: 'No matter what you think, we're going to go ahead and build centrifuges and preserve the option of going further'," Powell said.
"I would hope that the Japanese government and Japanese businesses would take this into account as they make judgments as to whether this is the place that one should be making investments in or doing this kind of energy business with," he said.
Earlier this year, the United States expressed "deep concern" over Japan's decision to participate in a two-billion dollar joint development project for Iran's massive Azadegan oil field.
"We remain deeply concerned about deals such as this and disappointed that these things might go forward," State Department spokesman Richard Boucher said in February.
The United States accuses of Iran of using its civilian atomic energy program as a cover for the secret development of nuclear weapons and has led a charge at the IAEA to press Tehran into admitting it and abandoning the aim.
Iran vehemently denies the US allegations.