A fundamental goal in cancer-associated genome sequencing is to identify the key genes. Protein–protein interactions (PPIs) play a crucially important role in this goal. Here, human reference interactome (HuRI) map was generated and 64,006 PPIs involving 9094 proteins were identified. Here, we developed aphysicallinkandco-expression combinatory network construction (PLACE) method for genes of interest, which provides a rapid way to analyze genome sequencing datasets. Next, Kaplan‒Meier survival analysis, CCK8 assays, scratch wound assays and Transwell assays were applied to confirm the results. In this study, we selected single-cell sequencing data from patients with hepatocellular carcinoma (HCC) in GSE149614. The PLACE method constructs a protein connection network for genes of interest, and a large fraction (80%) of the genes (screened by the PLACE method) were associated with survival. Then, PLACE discovered that transmembrane protein 14B (TMEM14B) was the most significant prognostic key gene, and target genes of TMEM14B were predicted. The TMEM14B-target gene regulatory network was constructed by PLACE. We also detected that TMEM14B-knockdown inhibited proliferation and migration. The results demonstrate that we proposed a new effective method for identifying key genes. The PLACE method can be used widely and make outstanding contributions to the tumor research field.