De Lille has received harsh criticism on social media for her mayoral committee being male dominated.
The African National Congress (ANC) has reportedly called the committee composition "a slap in the face of women".
Zille addressed the matter on the side lines of a women's month event in Cape Town this morning.
"It's very easy to deflect a lot of important debates in South Africa into the issues of quota but that misses the point. The challenge is to ensure that every woman has the opportunity to be the best she can be, and there are millions and millions of women in South Africa who don't get off first base."
In 2011 the premier herself faced criticism over her all male cabinet after a reshuffle.
At the time, Zille said she was ready and fully prepared for a potential barrage of criticism over the fact there were no women in her cabinet.
"Anything we do is criticised by the political analysts who work outside any form of constraint at all, so I completely accept that. They are within their rights to criticise," she said.
Two years earlier, the ANC Youth League claimed Zille appointed only men to her cabinet because she wanted "concubines". It also called her a "political prostitute".
The ruling party later rebuked its youth wing for making the inflammatory statements.