His owners say he had shown signs of heart problems ever since his "best friend" - a dog called Buddy - died in 2017.
"We think his heart literally broke when Buddy left us," they wrote on his official Facebook page.
Boo had 16 million followers on Facebook, made TV appearances, and even
released a book called Boo - the life of the world's cutest dog.
Boo and his friend Buddy had lived together for 11 years - before Buddy passed away in September 2017 at the age of 14.
His owners, who are from the US, say Boo passed away in his sleep early Saturday morning and they were "heartbroken".
They added: "But we find comfort knowing that he is no longer in any pain or discomfort.
"We know that Buddy was the first to greet him on the other side of that
rainbow bridge, and this is likely the most excited either of them have
been in a long time."
His owners went on: "Boo, we love you with all our hearts and will miss you until the day we meet again.
"Have fun running around with Buddy and creating adorable mischief wherever you guys go."
As well as releasing a book, Boo met with celebrities such as Seth
Rogan, became an ambassador for a US airline and appeared on several TV
shows in the US.
His owners said they'd received many notes over the years from people
sharing their stories of how Boo "brightened their days and helped bring
a little light to their lives during difficult times".
"And that was really the purpose of all this...Boo brought joy to people all over the world."
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