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. This study investigated the relationship between khat chewing and UDT cancers among male patients in Hargeisa using a case-control design. A total of 97 respondents were included, 36 cases and 61 controls from the only two cancer clinics in Somaliland, Nageeye Cancer Clinic and Needle Hospital. The study used non-probability purposive sampling, data collection was conducted using a structured questionnaire, and data entry and cleaning were performed using SPSS version 22. Analysis was carried out using Stata MP 16. The findings revealed an association between duration, frequency and amount of khat chewing and the risk of developing UDT cancers. Specifically, individuals who chewed khat for more than 20 years had a 7.05 times higher risk (p < 0.05), those who chewed daily had a 6.89 times higher risk (p < 0.05), and heavy chewers (>600 g) had a 6.60 times higher risk (p < 0.05) of developing UDT cancers. The associations found in this study between khat chewing and UDT cancers suggest an urgent need for public health strategies, including education and policy reforms, to address and reduce the health risks posed by khat chewing in Somaliland. The study also highlighted the importance of community education and awareness programs to mitigate the adverse health effects of khat.