Background: Non-Hodgkin lymphoma (NHL) is one of the major health problems worldwide, but the global burden and trends of NHL have not been extensively assessed. We aimed to describe the disease burden, risk factors, trends in incidence and mortality of NHL globally. Methods: We collected up-to-date incidence and mortality data of NHL from the GLOBOCAN 2020, focusing on geographic disparities worldwide. The incidence trends of NHL in 42 countries over 15 years were examined, while mortality trends of 39 countries were calculated by data extracted from cancer registries. Prevalence data from the World Health Organization database was used to estimate the attributable risk factors in the development of NHL. Future burden estimates for incidence and mortality in 2040 were calculated by applying population projections in 2020. We reported incidence and mortality by sex and age alongside corresponding age-standardized rates and the average annual percentage change. Results: In 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. The age-standardized incidence rates (ASIR) varied drastically across world areas, at least 10-fold in both sexes, with the highest rates observed in Australia and New Zealand. A great burden of NHL was recognized in high-income countries as the highest incidence rates were in Australia and New Zealand (ASIR, 12.5), Northern America (ASIR, 12.0), and Northern Europe (ASIR, 11.4) (Figure 1). Conversely, countries with a low human development index (HDI), such as those in North Africa, encountered a larger mortality burden in NHL than in highly-developed countries. In terms of different continents or regions, higher mortality rates were seen in Melanesia (ASR, 4.0), North Africa (ASR, 3.7), and Micronesia (ASR, 3.6). Considering the global trends of incidence, it was found that most developed countries had a trend of steady growth, while some low HDI countries have relatively large fluctuations in the incidence. In subgroups of different genders, close to 20 populations exhibited higher ASIRs for women than men. Observed trends also differed across age groups. The incidence of NHL increased in 34 populations (AAPCs, 4.9 to 0.1) among individuals aged 60 years or older. Taking into account differences in NHL burden across countries, we also reported estimated burden of NHL by HDI category. Considering all 185 countries, the ASIRs of NHL rose with HDI levels (= 0.41, P < 0.001), whereas the ASMRs of NHL were not associated with the levels of HDI (= 0, P = 0.754). HIV was generally believed to be a possible contributing factor to the development of some types of NHL, we presented the linear relation between the magnitude of the NHL incidence, HIV prevalence, and the level of HDI which seemly constricted to very high HDI countries. Regarding associated lifestyle risk factors, higher incidence of NHL was linked to a higher prevalence of obesity (β = 0.399, P < 0.001), a decreased prevalence of diabetes (β = -0.468, P <0.001) and hypertension (β = -0.386, P <0.001) based on the multivariate linear regression. As a result, countries with higher incidence were more likely to have a higher prevalence of obesity. In terms of demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040. Conclusions: In this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women and elderly populations. Despite the stable or downward mortality trends observed in most countries, the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed to cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal