Predation of livestock by wildlife and the retribution responses it elicits can have strong negative impacts on both people and carnivores. A questionnaire survey designed to investigate human-carnivore conflicts was completed by 66 herders from local communities within Taxkorgan Nature Reserve, located in the Pamir and Karkorum mountains of Northwestern China. A total of 127 livestock predation events with associated predator identification were reported and 583 livestock were killed. Wolves (315 livestock) and dholes (129 livestock) were responsible for the largest number of livestock losses. Livestock depredation significantly differed between guarded and unguarded management strategies. Positive relationships between loss and the total amount of the major livestock species, as well as the total loss and total amount of livestock, were detected. Use of guard dogs did not affect the likelihood of carnivore attacks, whereas keeping livestock in pens at night or all day did reduce the number of depredation events. Depredation showed significant seasonal variation (month of occurrence) for large carnivores. Numbers of goat, sheep, and cattle predated also varied by month, but did not for yak because of different husbandry practices. No compensation policy has yet been established in this area, but if it were to be developed in the future, 83% of interviewed herders would require compensation in cash, whereas 14% of herders would prefer replacement livestock. Our study offers suggestions to mitigate livestock depredation in this region of China. To prevent livestock depredations, local herders should mainly prevent wolves and dholes because they cause most livestock killings, and employ guarded grazing practice. Managers could make herders keep a reasonable number of livestock to raise grazing efficiency, introduce suitable sheepdog breeds, and provide essential dog training as useful aids to herders to increase livestock-guarding effectiveness.