The interview was published two days after the Baath party announced the names of 16 new leaders, which included none of the party's former chiefs with the exception of Assad, who will remain secretary general.
"When a leader does not solve a series of errors, this leader must be held accountable," Assad told Al-Baath newspaper, without elaborating.
"This is the real role of the (Baath party's) central committee, which is supposed to hold accountable the leaders on a regular basis. This did not happen in recent years," he added.
The reshuffle came more than two years into a brutal war that has left more than 100,000 dead in Syria.
"Those defending the nation now are the workers and farmers... Some of them are in the army, others defending their land," said Assad.
"The struggle now is between those who are ignorant and those who are aware, between the patriots and the collaborators, between extremists and moderates."
The Baath party has been in power since March 8, 1963.
Until February 2012, the Syrian constitution described the Baath as the ruling party of Syrian society.
The party's reshuffle was the first since 2005.
Among those removed from the party's leadership was Vice President Farouk al-Sharaa, the only top Syrian official to advocate a political compromise to the country's bloody civil war.
In the same interview Assad renewed his criticism of the Muslim Brotherhood, while saluting Lebanon's Shiite Hezbollah and Iran.
Ever since mass protests led to the removal from office of Egypt's Islamist president Mohamed Morsi, Assad and his government have launched numerous attacks on the Muslim Brotherhood.
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