Background: Khat chewing is a common cultural practice in countries bordering the Red Sea and the east coast of Africa. Despite some indications in the literature, its association with upper digestive tract (UDT) cancers is under-researched.

Methods: This case-control study investigated the relationship between khat chewing and UDT cancers among male patients in Hargeisa, Somaliland. A total of 97 participants (36 cases with UDT cancer and 61 controls) were recruited using purposive sampling from the two cancer clinics in Somaliland: Nageeye Cancer Clinic and Needle Hospital. Data were collected via structured interviewer-administered questionnaires. Analysis was performed using Stata/MP version 16.

Results: After adjusting for confounders, khat chewing was significantly associated with increased UDT cancer risk in a dose-response manner. Ever chewing khat was associated with an adjusted odds ratio (aOR) of 3.51 (95% confidence interval (CI) 1.23–11.2; p = 0.024). Chewing for >20 years had an aOR of 36.8 (95% CI 7.16–303; p < 0.001), daily chewing an aOR of 22.6 (95% CI 5.30–124; p < 0.001) and consuming >600 g per session an aOR of 6.87 (95% CI 2.06–25.8; p = 0.002).

Conclusion: These findings highlight a strong association between khat chewing and UDT cancers and underscore the urgent need for public health interventions, including awareness campaigns and policy measures, to mitigate khat-related cancer risks in Somaliland.