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Schefflera rubriflora, a plant native to Yunnan Province in China, is often used to treat ailments such as neuropathic pain, tracheitis, and cough. However, the active components imparting these pharmacological effects are largely unexplored. In this study, five novel lignans and three new derivatives of benzoid or pyran were isolated from the leaves and twigs of S. rubriflora. The structures of these compounds were determined by the comprehensive analyses of the 1D and 2D NMR spectra and ESI mass spectra and a comparison of the obtained data with those of the literature data. All the compounds were tested for the inhibition of IL-6 expression. Three of the isolated compounds could inhibit the expression by 52% to 72%.