Objective <p>To estimate mortality trends and disease burden of Digestive system cancer (DSC) in China during 2006–2020, using demographic and mortality data from cause-of-death surveillance dataset of China.</p> Methods <p>Joinpoint regression was applied to calculate the crude mortality rate (CMR), age standardized mortality rate (ASMR), annual percentage change (APC), and average annual percentage change (AAPC) for analyzing the trend of death change, and years of life expectancy lost (LLE) and early death lost life (YLL) were utilized to assess disease burden. Bayesian Age-Period-Cohort models were employed to project future mortality trends up to 2045.</p> Results <p>From 2006 to 2020, the combined ASMR and YLL rates for female DSC showed stability, with an average life expectancy loss of 7.06 years and the highest YLL rate in the 60–65 age group. Esophageal cancer, gastric cancer, and liver cancer showed a decreasing trend from 2015 to 2020, with APCs of -4.59% (<i>P</i> = 0.001), -5.25% (<i>P</i> = 0.002), and − 3.74% (<i>P</i> = 0.002), respectively. Colorectal cancer and pancreatic cancer showed an upward trend in 2016–2020, with APC of 1.85% (<i>P</i> = 0.021) and 2.74% (<i>P</i> = 0.023), respectively. The trend of standardized YLL rate changes was statistically significant (AAPC = − 2.8%, 95% CI: − 3.3%, 2.3%). The standardized YLL rates of esophageal cancer (AAPC=-5.0%, 95% CI: -5.6%, 4.5%), gastric cancer (AAPC = − 4.2%, 95% CI: − 4.8%, 3.7%), and liver cancer (AAPC = − 2.7%, 95% CI: − 3.3%, 2.2%) all showed a downward trend. By 2045, a significant downward trend in both death counts and ASMRs of DSC in China from 2006 to 2045 across all genders (<i>P</i>_trend&lt;0.001), with the most pronounced decline observed in males.</p> Conclusions <p>These findings reveal divergent trends in the distribution of DSC in China. Implementing gender-specific strategies, particularly for males, and strengthening cancer surveillance systems are crucial for sustained public health improvements.</p>