The aroma-active compounds and the levels of acrylamide and ascorbic acid in pan-fried potato slices cooked at three different temperatures (i.e., 160, 180 and 210C) and five heating times (i.e., 2, 4, 6, 8 and 12 min) were detected. The aroma-active compounds in potato slices were extracted by solid-phase microextraction and then analyzed by gas chromatography–olfactometry–mass spectrometry. A total of 26 aroma-active compounds were identified. The levels of acrylamide in potato slices were detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The acrylamide content of the potato slices increased with the increase of pan-frying time and temperature. The levels of ascorbic acid in potato slices were detected by HPLC. The retention rate of ascorbic acid also decreased with the increase of pan-frying time and temperature. The different processing conditions were evaluated after integrating the three aspects of food flavor, safety and nutrition. Practical Applications Fried food such as fried potato slices is deeply loved by consumers; however, due to high-temperature frying, it contains hazardous substances such as acrylamide, and the nutrient content such as ascorbic acid degrades to some extent. In this study, several frying conditions were evaluated comprehensively to find a balance point between best flavor, relatively lower acrylamide content (hazard) and higher retention rate of ascorbic acid (nutrient). This is meaningful to guide people to healthy diet, and it may provide evidence for the development of new technology of potato processing.