Genome-wide association studies in European and Asian populations have consistently identified chromosome 5p15.33 as a lung cancer susceptibility region. To investigate further the genetic architecture of common variants in this region, we conducted a two-stage fine-mapping analysis discovered by targeted resequencing of 200 cases and 300 controls individually, and validated in multiethnic lung cancer Genome wide association studies (GWASs) with 12,843 cases and 12,639 controls. Two independent variants were identified in approximate conditional analysis with GCTA and consistently validated in lung cancer GWASs in both Asian and European populations. These were rs10054203 inTERT(resequencing: OR = 1.69,p = 2.70 × 10−4; validation: OR = 1.34,p = 2.10 × 10−23 for Asian, and OR = 1.09,p = 6.00 × 10−3 for European), and rs397640 inCLPTM1L(resequencing: OR = 0.37,p = 1.19 × 10−4; validation: OR = 0.75,p = 5.89 × 10−8 for Asian, and OR = 0.90,p = 2.40 × 10−2 for European). Expression quantitative trait loci analysis showed the risk allele (C) of rs10054203 was significantly associated with lower mRNA expression ofCTD-2245Ef15.3(p = 0.019) andTubulin Polymerization-Promoting Protein(TPPP,p = 0.031) in 167 lung tissues. In conclusion, in this largest and first resequencing-based fine-mapping analysis of 5p15.33 region in Han Chinese, we identified two novel variants associated with lung cancer susceptibility. Further validation studies and functional work is required to confirm the roles of the newly discovered variants.