We present the possible adsorption sites of cyclooctyne on the biphenylene network, with distinct selectivity for the adsorption between the 6-and 4-ring. The finding opens the biphenylene network towards covalent functionalization. The thermodynamically favored adsorption is between the 6-and 4-ring. The reaction barrier for the [2+2] cycloaddition of the adsorption between 8-and 4-ring is slightly lower due to attractive dispersion interactions at the transition state and results from the high flexibility of cyclooctyne. The overall high reaction barrier originates from the strain necessary to deform the biphenylene network.