The surface uplift history of the Tibetan Plateau remains one of the most important unresolved issues in geosciences. Numerous models have been proposed to account for the growth of the Tibetan Plateau. This paper tries to analyze the surface uplift of the Tibetan Plateau from isostatic effects of the Cenozoic sedimentary accumulation. Based on isostatically-compensated basin infilling model, we show that the surface uplift magnitudes caused by the Cenozoic sedimentary accumulation constitute the main part of the modern elevations of the Qaidam and Tarim basins around the Tibetan Plateau, but only a small part of the modern elevations of the Hoh Xil and Lunpola basins inside the Tibetan Plateau. Paleogene sediments account for the uplift magnitudes of >900 m in both the Hoh Xil and Lunpola basins, while the uplift magnitudes caused by Neogene sediments are <100 m in these two basins. In contrast, the uplift magnitudes caused by Paleogene sediments in the Qaidam and Tarim basins around the Tibetan Plateau are relatively limited, whilst Neogene sediments contribute ~1100 m and ~700 m of their modern elevations respectively. It suggests that the central Tibetan Plateau was with high relief during the early Cenozoic, and its surface was successively flattened by erosion and basin-infilling processes. The initial uplift of the Tibetan Plateau occurred at the weak zones and the rigid blocks inside the Tibetan Plateau were gradually broken.