The purpose of this research was to determine the residue analysis of difenoconazole in apple fruits from Resen region, Republic of Macedonia. Analyzed were two varieties of apples, Golden Delicious and Idared. Samples were taken from two different locations in Resen in the year 2016. Difenoconazole analysis was performed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) after a previous extraction of residue by applying the QuEChERS method. The obtained concentrations of residues of difenoconazole are compared with the maximum residue limit regulated by the Macedonian legislation. Analyses showed that the concentration of difenoconazole in both varieties of apples from two different locations is in the range of 0.01 to 0.41 mg/kg. In certain development phase of the apple fruits the concentration reaches 80 times lower concentration than the maximum limit. The data show that apple fruits can be safely consumed according to the recommended maximum residue limit (MRL) for difenoconazole in apples (0.8 mg/kg). Statistical processing of the data suggests that there is no significant difference between samples but presence of difenoconazole in apple fruits from both locations is with significant difference.