His family announced his death on Wednesday, saying he faced his final days "with courage, faith and grace".
Van Der Beek rose to fame playing Dawson Leery in the popular US teen drama, which ran for six seasons from 1998 until 2003.
Co-star Busy Philipps paid tribute to her former co-star on Instagram, months after the cast reunited to help raise money for his cancer treatment.
"My heart is deeply hurting for all of us today," she wrote.
"Every person who knew James and loved him, anyone who loved his work or had the pleasure of meeting him, all of his dear friends and community that surrounded him as he battled this illness, especially his parents and brother and sister.
"But I am profoundly heartbroken for his incredible wife Kimberly and their six magical children.
"James Van Der Beek was one in a billion and he will be forever missed."
Sentiments were echoed by Kerr Smith, who starred alongside Van Der Beek for five seasons as Jack McPhee.
"I'm so grateful for being able to call James a brother," he said on Instagram, adding: "I'll miss him deeply. Rest Easy."
In September, the Dawson's Creek reunion event was organised in support of him and the charity F Cancer.
The night was attended by his former co-stars, including Michelle Williams, Katie Holmes and Joshua Jackson.
Van Der Beek had planned to be there but was too unwell.
His role was taken by Hamilton creator Lin-Manuel Miranda, who posted a picture of himself and Van Der Beek's family from the night on Instagram and said his "whole heart" was with them.
One Tree Hill actor Chad Michael Murray, who starred in Dawson's Creek for 12 episodes, described Van Der Beek as a "giant".
"His words, art and humanity inspired all of us - he inspired us to be better in all ways," Murray said under his family's Instagram statement.
Mary-Margaret Humes, who played Dawson's mother called Van Der Beek her "gracious warrior" and said she was at a "loss for words".
The series, which followed a group of friends through the trials of adolescence, became a cultural touchstone and launched Van Der Beek into international fame.
His film credits include the 1999 cult classic Varsity Blues, Jay And Silent Bob Strike Back, The Big Bang and Labour Day.
Van Der Beek was also known for playing a fictional version of himself in Don't Trust The B in Apartment 23.
Co-star Krysten Ritter called Van Der Beek "smart, funny, empathetic, kind, talented, and just pure magic", posting on Instagram that she was "so grateful for our friendship".
Numerous celebrities including Sarah Michelle Gellar, Ben Stiller, Selma Blair, Alec Baldwin, Melissa Joan Hart, Christie Brinkley and Rosie O'Donnell paid tribute to the Varsity Blues actor on social media.
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