The top businessman and TV celebrity will be joining pier owner Kerry Michael for the Sport Relief Mile on March 21.
The run will take place up and down the stretch of pier between the shore and the pier head, then along the beach to the SeaQuarium.
The new £51 million pier, which was destroyed by a fire in July 2008, will be open for the first time since rebuilding work started, so runners will get a sneak preview of the landmark that is due to open this summer.
The charity event, where people will choose whether to run one, three or six miles, will be screened on television.
All the money raised will go to Comic Relief to help transform the lives of poor and vulnerable people, both at home and across the world's poorest countries.
In the past, the event has been held at Hutton Moor Sports Centre, but this year the council agreed to relocate it to the tourist attraction so runners and spectators can get a sneak preview of the new pier and the seafront enhancement works.
Mr Paphitis, who is managing director of Ryman Stationery, is busy encouraging his 2,500 employees and their millions of customers nationwide to raise in excess of £100,000 for Sport Relief.
Mr Paphitis said: "Having recently returned from a trip to Kenya with fellow Dragons, where we saw the positive impact of money raised through Sport Relief, I am more determined than ever to raise loads of cash."
Contractors have been working since April on the pier rebuild and the landmark is due to open again in June. The new pavilion will be home to 500 different skill machines and 18 new rides, which alone have cost just over £5m.
There will also be 29 different new outlets on the ground and first floor, ranging from coffee shops and restaurants to gift shops.
The pier will be an all-year-round attraction.