The two-volume set LNCS 10769 and 10770 constitutes the refereed proceedings of the 21st IACR International Conference on the Practice and Theory of Public-Key Cryptography, PKC 2018, held in Rio de Janeiro, Brazil, in March 2018. The 49 revised papers presented were carefully reviewed and selected from 186 submissions. They are organized in topical sections such as Key-Dependent-Message and Selective-Opening Security; Searchable and Fully Homomorphic Encryption; Public-Key Encryption; Encryption with Bad Randomness; Subversion Resistance; Cryptanalysis; Composable Security; Oblivious Transfer; Multiparty Computation; Signatures; Structure-Preserving Signatures; Functional Encryption; Foundations; Obfuscation-Based Cryptographic Constructions; Protocols; Blockchain; Zero-Knowledge; Lattices.