Zak Damarell scored a hat-trick as the islanders beat London Edwardians 3-1 in their second-round tie in the capital.
"It's enormous," Guernsey coach Andy Whalley told BBC Sport.
"They're an unbelievable side, they've been European champions, their pedigree is great, everyone knows Reading."
Guernsey went a goal down inside the first 10 minutes of their second-round tie, but Damarell's first goal ensured it was level at half-time.
Guernsey had to weather huge pressure from their hosts, with Adrian Gidney making a string of important saves in goal, as Damarell twice scored on the break.
The island side is made up of players from the Guernsey league and does not play in a league itself.
But they have a fine pedigree in the second-tier EH Trophy, making the last five finals, winning twice.
"We've got an awful lot of work to do, but we're excited and looking forward to it," added Whalley.
"It's a game we're not expected to win, they'll be massive favourites, but you never know what might happen on the day - we've got some wonderfully talented players in our squad."
Guernsey's hockey team have secured the biggest match in their history after progressing to the third round of the England Hockey Cup to face Premier League side Reading.