Rejecting calls, notably by France, to halt the negotiations on the Transatlantic Trade and Investment Partnership (TTIP), Moscovici told reporters in Paris: "It would be much smarter... to pursue them, while raising our demands."
He appealed for support from the trade ministers of EU member states for the TTIP, which has become a hot potato as key elections approach in the United States, France and Germany.
The talks - conducted in secret between the EU executive body and US negotiators - have become bogged down as suspicions abound in Europe that the deal would undercut the 28-nation bloc's standards in key areas such as health and welfare.
Moscovici's remarks came after French junior trade minister Matthias Fekl said Paris wanted to halt the talks, saying US negotiators were offering "nothing or just crumbs".
French President Francois Hollande and Prime Minister Manuel Valls have also thrown cold water on the negotiations, with Valls on Thursday demanding a "clear halt".
Germany's vice chancellor and economy minister Sigmar Gabriel said the talks had "de facto failed because we Europeans of course must not succumb to American demands."
His boss Angela Merkel however spoke out in favour of a deal, saying it would create "job opportunities" for Europe.
Hollande and Merkel were due to meet later this Friday at the French town of Evian-les-Bains, ahead of the 25th Franco-German talks, which will include the participation of senior business leaders from both countries.
- with AFP