Objective To explore the effect and mechanism of Linc01135 on the proliferation and differentiation of osteoblasts and oxidative stress injury induced by hydrogen peroxide. Methods Human osteoblast hFOB 1.19 were divided into Con group, H2O2 group, H2O2+pcDNA group, H2O2+pcDNA-Linc01135 group, H2O2+pcDNA-Linc01135+SB203580 group. Methyl thiazolyl tetrazolium assay (MTT) was used to detect cell viability. The flow cytometry was used to detect cell cycle and apoptosis. Western blot method was used to detect Runt related genes 2 (Runx2) and osteocalcin (OCN), cleaved cysteine containing aspartate-specific proteases-3 (Cleaved-caspase3), caspase3 precursor (Pro-caspase3), phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) protein expression. The kits was used to detect superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content. The real time fluorescence quantitative PCR (RT-qPCR) to detect the expression of Linc01135. Results The OD value of osteoblasts affected by hydrogen peroxide was decreased. The proportion of G0-G1 phase cells was increased, the proportion of S phase cells was decreased. The expressions of Runx2 and OCN proteins were decreased, and the apoptosis rate was increased. Cleaved-caspase3 expression was increased, Pro-caspase3 expression was decreased. T-AOC and SOD activity were decreased, MDA content was increased, Linc01135 expression was decreased, p-p38MAPK protein expression was decreased (P＜0.05). After overexpression of Linc01135, the OD value of osteoblasts was increased, the proportion of cells in G0-G1 phase was decreased, the proportion of cells in S phase was increased, the expressions of Runx2 and OCN protein were increased, and the apoptosis rate was decreased. Cleaved-caspase3 expression was decreased, Pro-caspase3 expression was increased, T-AOC and SOD activity were increased, MDA content was decreased, p-p38MAPK protein expression was increased (P＜0.05). The p38MAPK signaling pathway blocker can attenuate the effects of Linc01135 on the proliferation and differentiation of osteoblasts and oxidative stress injury induced by hydrogen peroxide. Conclusion Over expression of Linc01135 may promote the proliferation and differentiation of osteoblasts by activating p38MAPK signaling pathway, and inhibit the apoptosis and oxidative stress damage of osteoblasts induced by hydrogen peroxide.