The effects of seed size and drought stress on the growth and physiological characteristics of Quercus wutaishanica seedlings were investigated under shading conditions of a pot experiment in greenhouse. There were four treatments, including 80% field water content (FWC), 60% FWC, 40% FWC, and 20% FWC [CK, light drought stress (LDS), medium drought stress (MDS), and high drought stress (HDS), respectively]. The results showed that leaf area per plant, total dry mass, and root-shoot ratio of Q. wutaishanica seedlings regenerated from large seeds (3.05±0.38 g) were significantly higher than those from small seeds (1.46±0.27 g) in all four treatments. Shoot height, basal stem diameter, leaf number, specific leaf area, relative growth rate, and net assimilation rate of the seedlings from large seeds were higher than those of seedlings from small seeds under the treatments of LDS, MDS and HDS. Activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) in large-seeded seedlings were higher than those of small-seeded seedlings under all treatments, while the contents of MDA, soluble protein, free proline, and total chlorophyll of large-seeded seedlings were higher than those of small-seeded seedlings only under some drought stress treatments. All growth parameters except the root-shoot ratio decreased with the increases of drought stress. The HDS treatment resulted in 19.4% and 20.0% decline in total dry mass of large- and small-seeded seedlings respectively, compared with those of CK. With increasing drought stress, the activities of POD, CAT, and SOD decreased after an initial increase. POD activity of large- and small-seeded seedling under MDS treatment was 126.7% and 142.1% higher than CK, while CAT was 170.0% and 151.9% higher than CK, respectively. However, the MDA content of seedlings from large and small seeds under HDS treatment was 86.5% and 68.9% higher than that of CK, respectively. The contents of soluble protein, free proline, and total chlorophyll rose at first and then fell with increasing drought stress, and soluble protein content in large- and small-seeded seedlings experienced MDS enhanced 320.7% and 352.7%, respectively. Those results indicated that large-seeded seedlings of Q. wutaishanica had stronger drought tolerance than small-seeded seedlings due to their growth and physiology advantages. Large-seeded seedlings with stronger resistance to drought stress should be applied to artificial regeneration of the degraded secondary Q. wutaishanica plantations.