The champions head to Vitesse on Sunday facing what will be a nine-point gap to PSV if the leaders beat Willem II the day before.
Ajax have only lost twice in the league this season, but last weekend's goaless draw against Feyenoord saw them fall further off the pace and De Boer recognises that their title defence has reached a crucial stage.
"Six points is the maximum [gap]," De Boer told the club's official website. "We put ourselves under pressure with a draw against Feyenoord.
"Nothing can go wrong now, it is obviously more difficult, you get more difficult matches."
Added to the significance of a win is the opportunity for revenge after Vitesse knocked Ajax out of the Dutch Cup with a comprehensive 4-0 win in December.
PSV will be confident of making it seven top-flight wins in a row when they host Willem II, having scored three goals against Saturday's visitors in each of the last three meetings and not lost to since 2004.
Like Vitesse, Willem II have seen recent poor form put a dent in their hopes of a top-eight finish, which would secure a UEFA Europea League play-off berth.
Third-placed Feyenoord have their eyes on Europe's premier club competition and they host struggling ADO Den Haag.
Rock-bottom Dordrecht breathed new life into their campaign with a 1-0 win over Excelsior last time out - just their second of the season - and they welcome Heerenveen.
NAC Breda sit one place and four points above Dordrecht, with Excelsior up next for Robert Maaskant's side.
Maaskant has been boosted by the arrival of Ajax full-back Ruben Ligeon on loan until the end of the season and the 22-year-old is expected to make his debut this weekend.
Elsewhere, Heracles visit AZ, fourth-placed PEC Zwolle travel to Utrecht, Groningen host Go Ahead Eagles, and sixth plays eighth as Twente welcome Cambuur to Enschede.
Thank you for reading 5 articles this month* Join now for unlimited access
Enjoy your first month for just £1 / $1 / €1
*Read 5 free articles per month without a subscription
Join now for unlimited access
Try first month for just £1 / $1 / €1
Get FourFourTwo Newsletter
The best features, fun and footballing quizzes, straight to your inbox every week.