The Erhualian pig, originally distributed in the Taihu area, is well known for its universally high fertility. Previous studies have found that high ovulation numbers, low embryo mortality and high uterine volumes are important physiological characteristics underlying the high prolificacy of the Erhualian pig. Although candidate genes such as follicle-stimulating hormone β (FSHβ) and several quantitative trait loci (QTLs) on chromosome 2, 6, 7, 8, 12, 13 and 15 have been reported to affect the litter size in the Erhualian pig, the key genes related to high prolificacy remain poorly understood. In this review, we summarize the recent research progress in the physiological and genetic mechanisms underlying the high prolificacy of the Erhualian pig. First we review the role of high ovulation numbers, low embryo mortality rates and high uterine volumes in the formation of the high litter size in the Erhualian pig. Then we summarize candidate genes and QTLs for the high litter size detected by classical strategies, as well as by genomic strategies. Moreover, we describe the methods to investigate the causative genes of the high prolificacy through integrative analysis of multi-omics data including genomics, transcriptomics, proteomics and functional genomics. This review will provide insights to understand the molecular basis of the high prolificacy in the Erhualian pig.