Fruit cracking has long been a topic of great concern for growers and researchers of litchi (Litchi chinensis Sonn.). To understand the molecular mechanisms underlying fruit cracking, high-throughput RNA sequencing (RNA-Seq) was first used for de novo assembly and characterization of the transcriptome of cracking pericarp of litchi. Comparative transcriptomic analyses were performed on non-cracking and cracking fruits. A total of approximately 26 million and 29 million high quality reads were obtained from the two groups of samples, and were assembled into 46,641 unigenes with an average length of 993 bp. These unigenes can be useful resources for future molecular studies of the pericarp in litchi. Furthermore, four genes (LcAQP, 1; LcPIP, 1; LcNIP, 1; LcSIP, 1) involved in water transport, five genes (LcKS, 2; LcGA2ox, 2; LcGID1, 1) involved in GA metabolism, 21 genes (LcCYP707A, 2; LcGT, 9; Lcβ-Glu, 6; LcPP2C, 2; LcABI1, 1; LcABI5, 1) involved in ABA metabolism, 13 genes (LcTPC, 1; Ca2+/H+ exchanger, 3; Ca2+-ATPase, 4; LcCDPK, 2; LcCBL, 3) involved in Ca transport and 24 genes (LcPG, 5; LcEG, 1; LcPE, 3; LcEXP, 5; Lcβ-Gal, 9; LcXET, 1) involved in cell wall metabolism were identified as genes that are differentially expressed in cracked fruits compared to non-cracked fruits. Our results open new doors to further understand the molecular mechanisms behind fruit cracking in litchi and other fruits, especially Sapindaceae plants.