The stoloniferous hydrozoan Obelia geniculata commonly colonizes macroalgae such as Saccharina japonica . Each Obelia colony consists of thread-like hydrorhizae attached to the seaweed thallus. The early signaling proteins of epiphytic contamination can be identified using proteomics. To isolate these early signals, parts of the thallus proximal to the hydrozoans were separated from beneath the colony front and from healthy tissue. From the proteomic profiles of S. japonica , we detected 110 protein spots from tissue proximal to hydrozoan colonies (56 increased, 53 decreased, and 1 unchanged in expression relative to healthy tissue) and 133 spots from tissue at the colony front (67 increased, 60 decreased, and 6 unchanged in expression). Of the proteins with increased and decreased expression, SIPA1L1 and actin increased strongly only in the proximal tissues, while NEK2 kinase decreased. CIPK20 and SIPA1L2 increased markedly in both the colony-front and proximal tissues, while CaMK2N2 and GK25369 decreased in both tissues. ATPase β, ADA, kinesin, and HECT domain proteins increased only in the colony-front tissues. Among them, SIPA1L2 increased strongly in both the thallus tissues proximal to the hydrozoans and those beneath the colony front, but was not expressed in response to bryozoan infection.