Quantifying the effects of alpine GMB (Glacier Mass Balance) on river runoff is an important content of climate change. Uncertainty exists in GMB monitoring when applying remote-sensing technology. There are several reasons for these uncertainties, such as terrain deviation co-registration among different topographic data, the mismatch between GSE (Glacier Surface Elevation) from satellite monitoring and the GMB that comprises the physical glacier properties, the driving factors of GMB, and the response patterns of the runoff within the basin. This paper proposed a method based on the ridge line co-registration of DEMs (Digital Elevation Models), and the Tailan River basin, which is a typical glacier melt runoff recharge basin located in the southern Tianshan Mountains, was selected. Abnormal values in GSE changes were removed using ice thickness data, and the GSE results were optimized based on the regularity of the GSE change with altitude to estimate the GMB. The driving factors of the GMB and the response characteristics of the runoff in the basin were also explored. The results showed that the accuracy of the optimized GSE results across different periods has improved by more than 25%. The mean annual thinning value of GSE in the basin from 2000 to 2022 was −0.25 ± 0.02 m·a−1, corresponding to a GMB value of −0.30 ± 0.02 m w.e.a−1, indicating a consistent GMB loss state. Combined with climate data, the glaciers in the basin were impacted by rising temperatures, and the smallest increase in annual precipitation in the basin was insufficient to compensate for the GMB loss. Moreover, in the past 22 years, glacier meltwater accounts for 46.15% of the total runoff in the Tailan River basin.