The 71-year-old actor posted the image on Instagram, showing him holding Jett Travolta in his arms as the boy reached for his father's ears.
Jett, who was the eldest child of Travolta and Kelly Preston, died at age 16 in 2009 after suffering a seizure while the family were on holiday in the Bahamas.
"Happy birthday Jett - I miss you so much! Love you forever!" he captioned the image.
Jett had a history of seizures and had been diagnosed with autism before his death.
Travolta and Preston also had daughter Ella Bleu Travolta and son Benjamin Travolta.
The actor said the loss of Jett was the most devastating moment of his life.
Speaking at a panel in 2014, he said: "The truth is, I didn't know if I was going to make it. Life was no longer interesting to me, so it took a lot to get me better."
Jett's sister, 25, also paid tribute on social media to the boy, sharing a photograph of their mother kissing Jett as a young child.
She captioned her image on Instagram: "Happy Birthday, Jetty. I love you so much."
Travolta has continued to honour his son's memory, not only with annual birthday tributes but also through the creation of the Jett Travolta Foundation, which supports children with special needs.
The Travolta family experienced another loss in 2020 when Preston died following a two-year battle with breast cancer aged 57.
She and John had been married since 1991.
Announcing her death at the time, the actor said: "She fought a courageous fight with the love and support of so many. Kelly's love and life will always be remembered."
Travolta continues to raise his youngest son, Benjamin, now 14.