BACKGROUND: For the reason that many studies have been inconclusive on the effect of humidity on respiratory disease, we examined the association between absolute humidity and respiratory disease mortality and quantified the mortality burden due to non-optimal absolute humidity in Guangzhou, China. METHODS: Daily respiratory disease mortality including total 42,440 deaths from 1 February 2013 to 31 December 2018 and meteorological data of the same period in Guangzhou City were collected. The distributed lag non-linear model was used to determine the optimal absolute humidity of death and discuss their non-linear lagged effects. Attributable fraction and population attributable mortality were calculated based on the optimal absolute humidity, defined as the minimum mortality absolute humidity. RESULTS: The association between absolute humidity and total respiratory disease mortality showed an M-shaped non-linear curve. In total, 21.57% (95% CI 14.20 ~ 27.75%) of respiratory disease mortality (9154 deaths) was attributable to non-optimum absolute humidity. The attributable fractions due to high absolute humidity were 13.49% (95% CI 9.56 ~ 16.98%), while mortality burden of low absolute humidity were 8.08% (95% CI 0.89 ~ 13.93%), respectively. Extreme dry and moist absolute humidity accounted for total respiratory disease mortality fraction of 0.87% (95% CI - 0.09 ~ 1.58%) and 0.91% (95% CI 0.25 ~ 1.39%), respectively. There was no significant gender and age difference in the burden of attributable risk due to absolute humidity. CONCLUSIONS: Our study showed that both high and low absolute humidity are responsible for considerable respiratory disease mortality burden, the component attributed to the high absolute humidity effect is greater. Our results may have important implications for the development of public health measures to reduce respiratory disease mortality.