Mark Flannagan, chief executive of Beating Bowel Cancer, is to stand down at the end of the month after six and half years in the role.
Third Sector columnist Flannagan said it had been a tough decision to leave "one of the best jobs in the sector", but the time was right for him to move on.
He said he planned to take a short break before considering his next career move.
Sir Christopher Pitchers, chair of Beating Bowel Cancer, said Flannagan had made an enormous contribution to the charity and the board was sad to see him go.
He said: "Mark has moved the charity on with a new focus on delivery to all those affected by bowel cancer, he has expanded our reach to help thousands more people and he has put Beating Bowel Cancer at the heart of government decision-making so that we are now further forward to saving more lives than ever before.
"His skills as a communicator have resulted in a hugely increased profile for bowel cancer and the charity."
Judith Brodie, deputy chief executive of Beating Bowel Cancer, will become acting chief executive while Flannagan’s successor is sought.