Two pills a day for two years reduced the incidence of bowel cancer by 63% in a group of 861 at-risk patients, a study reported in The Lancet said.
Newcastle University's Prof Sir John Burn, who led the study, said the evidence "seems overwhelmingly strong".
Other experts said the findings added to a growing body of proof that aspirin could be used in the fight on cancer.
The study was conducted on 861 patients with Lynch syndrome, which affects one in every 1,000 people.
They struggle to detect and repair damaged DNA which means they are more likely to develop a range of cancers including those of the bowel, womb and stomach.
'Good deal'
When looking at all patients in the trial, those in the group given 600 milligrams of aspirin every day developed 19 tumours compared to 34 tumours in the other "control" group, a reduction of 44%.
When the researchers looked at just those patients who took the medication for at least two years the reduction was 63%.
There was also an effect on other cancers linked to Lynch syndrome, which fell by half in the treatment group.
Prof Sir John Burn, from Newcastle University, said there were 30,000 adults in the UK with Lynch syndrome.
If all were given the treatment he said it would prevent 10,000 cancers over 30 years and he speculated that this could possibly prevent 1,000 deaths from the disease.
However, there would also be side effects.
"If we can prevent 10,000 cancers in return for 1,000 ulcers(溃疡) and 100 strokes, in most people's minds that's a good deal," he said.
"People who've got a clear family history of, particularly, bowel cancer should seriously consider adding low dose aspirin to their routine and particularly those people who've got a genetic predisposition."
Aspirin is already well known to reduce the risk of heart attack and stroke in high risk patients.
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