Sweeteners play an irreplaceable role in daily life and are also common additives in e-liquids. Study of the composition and monitoring of the content of sweeteners is significant for the product quality control of e-liquids. In this study a new method has been developed to detect four artificial sweeteners (aspartame, advantame, neotame and saccharin) in e-liquids simultaneously by ultra performance liquid chromatography (UPLC) combined with diode array detector (DAD). The separation effect and determination sensitivity of target compounds in this method were improved by exploring different chromatographic conditions, including the type of mobile phases, pH, and temperature. Under the condition of ACQUITY UPLC HSS T3 (100 mm × 2.1 mm, 1.8 µm), the conditions for analysis and detection have been optimized. Mobile phase is acetonitrile-20 mmol/L ammonium acetate aqueous solution, with the pH of 4.5 and temperature of 35 °C. The linearity coefficients of target compounds were > 0.999. The LOQs of analytes ranged between 0.0268 and 0.2127 mg/g and the mean recoveries were in the range from 92.5 to 108.3 %. After validation, the method was applied to detect the artificial sweeteners in 10 kinds of e-liquids with fruit, tobacco, and mint flavour characteristics. Sweeteners were found in most of the e-liquids except the tobacco flavour one. And the most detected target compound was neotame. The results have shown the good performance of the method because of its sensitivity, accuracy, effectivity and convenience.