Thirteen new linear terpenes, including 11 rare acyclic manoalide derivatives (1-11), one polyprenylphenol derivative (12), and one polyprenylbenzaldehyde derivative (13), together with three known compounds (14-16) were isolated from the sponge Luffariella variabilis collected in the South China Sea. The planar structures were resolved by NMR and MS analyses, while the absolute configurations were fully elucidated by NOESY experiments, combined with experimental and calculated ECD spectra, acetal formation, empirical rules of 1H and 13C NMR shifts, DP4+ probability analyses, and Mosher's method. Compounds 1-7, 10, and 13 demonstrated cytotoxic activities against several human cancer cell lines with IC50 values ranging from 2 to 10 μM.