International Friendly: Netherlands v Japan
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 FIFA 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 - second only to Germany in European qualification.
The hosts will be without Feyenoord midfielder Jordy Clasie as well as Van Persie for the Japan match and Van Gaal wants to see how his team cope without their star striker.
"We have to show how we are when he's not available," he said. "That could always be a scenario in Brazil.
"Because (Ricky) Van Wolfswinkel and (Klaas-Jan) Huntelaar are injured, we don't have many strikers. They are the ones behind Van Persie, but that can change if someone steps up now.
"Siem de Jong is a back-up plan in case of emergency, just like he is at Ajax. (Jeremain) Lens is also an option as central striker, especially when we come ahead in a match. It's nice to experience something like this so we can solve a problem."
Japan booked their place at the World Cup in June, finishing top of Group B in Asian qualifying, four points clear of second-placed Australia.
Following their 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 Netherlands game and their trip to Brussels to face Belgium on Tuesday.