The Manchester United man withdrew from the squad due to injury and, with Klaas-Jan Huntelaar and Ricky van Wolfswinkel also out, Louis van Gaal faces a selection dilemma.
Van Persie broke Patrick Kluivert's national goalscoring record in the 8-1 win over Hungary in October, but will not be fit for Saturday's clash in Genk or the visit of Colombia to Amsterdam on Tuesday due to toe and groin injuries.
The Manchester United striker has six goals from his last four appearances in the national team, with all of them coming in Netherlands' dominant World Cup qualifying campaign, and now has 41 in total.
Louis van Gaal's men dropped just two points in their 10 qualifiers, scoring 34 goals in the process - a goal total second only to Germany in European qualification.
Japan booked its place at the World Cup in June, finishing top of Group B in Asian qualifying, four points clear of second-placed Australia.
Following the team's successful progression, Alberto Zaccheroni's men clinched the East Asian Cup in July but have lost three of five friendlies since then.
After going down 4-2 to Uruguay in August, Japan beat Guatemala and Ghana 3-0 and 3-1 respectively before losing twice in Europe in October, suffering defeats to Serbia and Belarus.
Between them, Shinji Kagawa, Yasuhito Endo, Keisuke Honda and Masato Kudo have scored Japan's last eight goals, with only the latter not in the squad for the Oranje game and the trip to Brussels to face Belgium on Tuesday.