Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, has been found to possess protective effects against cancer development in the Western populations. Such effects among Asian populations remain uncertain. The objective of this study is to investigate the use of aspirin on prevention of different cancers among Chinese users. This population-based study utilized database from the Hong Kong Hospital Authority; adults with aspirin prescription for at least 6 months between 2000 and 2004 were included and followed up until 2013. Aspirin users were age-sex matched with non-aspirin users at a 1:2 ratio. Incidences of cancer were the primary outcome measured by relative risk (RR). A total of 204,170 aspirin users and 408,339 non-aspirin users were included, with the mean age 67.5 years, 7.7 years average duration of aspirin prescription and 80 mg as the median dose of aspirin. Cancer incidences were found in 26,929 (13.2%) aspirin users and 70,755 (17.3%) non-aspirin users. Compared with patients who had not been prescribed aspirin, aspirin usage led to significant reduction of cancers in liver (RR: 0.49), stomach (RR: 0.42), colorectum (RR: 0.71), lung (RR: 0.65), pancreas (RR: 0.54), oesophagus (RR: 0.59) and leukaemia (RR: 0.67). There was no demonstrable reduction of kidney cancer, bladder cancer, prostate cancer and multiple myeloma in association with the usage of aspirin. Risk of breast cancer was shown to marginally increase (RR: 1.14) with aspirin usage. This study demonstrated that the long-term use of low-dose aspirin is associated with the reduction in risk of various cancers but not for breast cancer. Further investigation is needed before promoting aspirin as a primary chemoprotective agent.