Reverse genetic analysis was performed on the Caenorhabditis elegans 26S proteasome subunit genes by double-stranded RNA-mediated interference (RNAi). Embryonic and post-embryonic lethality was caused by interference of all of the eight tested 20S core subunits and all of the 19S regulatory particle subunits except for Ce-Rpn9, Ce-Rpn10, and Ce-Rpn12, where RNAi caused no abnormality. However, synthetic suppression of Ce-Rpn10 and Ce-Rpn12 was lethal, whereas neither the combination of Ce-Rpn9 with Ce-Rpn10 nor with Ce-Rpn12 resulted in abnormalities in RNAi. These results indicate that the 26S proteasome is indispensable for embryogenesis and post-embryonic development, although Ce-Rpn9, Ce-Rpn10, and Ce-Rpn12 are not essential, at least under the conditions used. Ce-Rpn10 and Ce-Rpn12 are considered to compensate for the suppression of each other.