<i>Background/Aims:</i> Nutrigenomics is providing molecular biomarkers concerning the assessment of diet-related diseases. We analyzed the expression of two interacting genes (RIPK3 and RNF216) in obese subjects receiving a low-calorie diet (LCD) and during the subsequent weight changes. <i>Methods:</i> Two groups of obese subjects (BMI 32.3 ± 5.5kg/m²; age 37.7 ± 7.1 years) were selected according to the 6-month weight-regain outcome after the weight-loss induced by an 8-week LCD (n = 12). Body composition and mRNA levels of RIPK3 and RNF216 in peripheral blood mononuclear cells (PBMC) were evaluated by qRT-PCR at three time-points (week 0, week 8 and week 32). <i>Results: </i>All subjects lost weight significantly (–5.8 ± 2.3%, p < 0.001) and were grouped depending on the successful weight-loss maintenance (weight-loss regain ≤10% or >10%). At baseline (week 0), no differences were observed in the mRNA levels between groups (p > 0.05). However, at the end of the LCD (week 8), association analysis revealed that higher mRNA levels in PBMC of RIPK3 and RNF216 were able to detect those individuals who are more prone to regain weight 6-month after the nutritional intervention (p < 0.05). <i>Conclusions: </i>Gene expression of RIPK3 and RNF216 in PBMC could identify those obese subjects, who will regain more weight after a successful initial weight loss. The mRNA levels of these genes could be suggested as nutrigenomic biomarkers for predicting the obesity treatment outcome.