Guardian News & Media, which publishes the Guardian and the Observer, announced last week that it would need to make savings of £25 million over the next five years after sustaining losses of £33 million in the last financial year.
GNM employs 1,500 staff in total, with 630 of those journalists.
Rusbridger told the BBC Radio 4's The Media Show today: "Yes, we will need to lose some people and will try to do it in a voluntary way, but we need to end up employing fewer people than we do at the moment."
He added: "We will need to lose significant numbers but we don't need to do it by tomorrow. We can do it over the next couple of years and we can have a civilised conversation about that."
Rusbridger also said the Guardian would be seeking to take on more developers and people with digital skills as part of the planned shift.
"The blunt truth is that we don't have enough developers, we don't have enough people who know about mobile, who know about flash and data, multimedia. We need to get more of those and spend more of our day thinking about those kinds of our journalism."
In an announcement to staff last week, Andrew Miller, chief executive of GNM parent company Guardian Media Group, said GMG was seeking a "major transformation" at the titles and warned that the company could run out of cash in three to five years if business operations did not change.
Responding to speculation about job cuts following the announcement, a spokesperson for the group said: "Of course no media company can rule out redundancies in the current climate, but we will talk to staff about issues like that first."
According to last week's announcement, GNM aims to double digital revenue from £47m in the current financial year to £91m in five years' time.
ABC figures for April saw circulation of the Guardian drop 12.5 per cent year-on-year to 262,937, and the Observer fell 13.9 per cent to 293,053.
Digital traffic is up however, with 2.4 million unique users in April, a 31 per cent increase year-on-year.
Overall turnover for GMG was £221 million in the 2009/2010 financial year, with around £40 million of that coming from digital. That figure dropped by £23 million in 2010/2011 to £198 million.
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