PURPOSE: With a high HIV adult prevalence, the burden of cancer in Botswana has surged over the years, posing a significant threat for people living with HIV (PLWH). While HIV/AIDS-related deaths have declined due to effective antiretroviral therapy (ART), PLWH remain at elevated risk for cancer and related mortality. We aimed to evaluate all-cause mortality after cancer diagnosis among people with and without HIV in Botswana. METHODS: We included adults aged ≥ 18 years who were reported in the national cancer registry between 1990 and 2021. The crude, age-standardized mortality (ASMR) rates per 100,000 and standardized mortality ratios (SMRs) were calculated. We determined time trends using generalized linear regression, assuming a Poisson distribution. RESULTS: Over 30 years, 27,726 cancer cases and 9,609 deaths were reported. Of all the deaths, 4,548 (47.3%) were among PLWH, 1,183 (12.3%) among people without HIV, and 3,878 (40.4%) among people with unknown HIV status. Compared with people without HIV, the ASMRs for PLWH were higher and increased significantly from 1990 to 2021 (from 12.5 to 297.9 per 100,000, respectively; p-trend < 0.001) versus people without HIV (from 0.4 to 7.3 per 100,000, respectively; p-trend = 0.006). Further, mortality rates rose among PLWH who had AIDS-defining cancers (ADCs), non-AIDS-defining cancers (NADCs), breast and cervical cancers (p-trend < 0.001). Although the SMRs for all ADCs and most NADCs sub-types declined after ART roll-out, in the late post-ART period, these were in excess among PLWH. CONCLUSION: Increasing trends and excess mortality among PLWH with cancer suggest a greater need for targeted screening strategies, and the provision of access to timely HIV and cancer treatment.