Background. Family history of diabetes (FHD) and lifestyle are associated with type 2 diabetes (T2DM), but little is known about the FHD diet interactions. We aimed to analyze the interactions of FHD and lifestyle factors in Chinese T2DM onset. Methods. This was a cross-sectional survey in central urban China (n = 1234 patients with T2DM and n = 8615 non-T2DM subjects). The biological interactions, defined by Rothman interactions, between FHD and each dietary factor were analyzed by using the synergy index (S) scores. Results. After adjustment for age, gender, BMI, and WHR, a uniparental FHD (OR = 2.84, 95% CI: 2.36-3.42, P < 0.001), a paternal history of FHD (OR = 2.53, 95% CI: 1.91-3.35, P < 0.001), a maternal history of FHD (OR = 3.27, 95% CI: 2.67-4.02, P < 0.001), a biparental history of FHD (OR = 5.26, 95% CI: 2.98-9.31, P < 0.001), and a FHD, irrespective of the parent (OR = 3.59, 95% CI: 3.08-4.17, P < 0.001), were associated with T2DM onset. There were significant interactions between FHD and consuming <15 g/d of potatoes (S = 1.54, 95% CI: 1.12-2.12), <8 g/d of poultry (S = 1.51, 95% CI: 1.04-2.17), <85 g/d of fresh fruits (S = 2.17, 95% CI: 1.63-2.88), and no freshly squeezed juice (S = 2.25, 95% CI: 1.46-3.49). Conclusions. Risk of T2DM was synergistically affected by FHD and dietary habits. Nutrition educational intervention may decrease the prevalence of T2DM in the Chinese with FHD.