Guidolin was hospitalised with a chest infection before their 2-1 away win over Arsenal on March 2 and missed his team's 1-0 home victory over Norwich City and 3-2 defeat by Bournemouth the following weekends.
"We have an important game on Saturday, and it the most important game of the season for us," the 60-year-old Italian told a pre-match news conference.
"We have to play well and we hope to get a good result to take into the last part of the season."
Seven-times champions Villa are last in the 20-team league, eight points behind 19th-placed Newcastle United and nine from safety.
"I know their situation, and I know how difficult matches like this can be," Guidolin added. "But I hope to see my team play well, with concentration and intensity."
(Reporting by Simon Jennings in Bengaluru; Editing by John O'Brien)
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