Objective.　Conditionally　replicating　adenoviruses　(CRAds)　have　been　proven　potent　oncolytic　viruses　in　previous　studies.　They　selectively　replicate　in　the　tumor　cells　because　of　incorporated　survivin　promoter　and　ultimately　lead　to　their　killing　with　minimal　side　effects　on　normal　tissue.　Chemotherapy　with　cisplatin　is　commonly　employed　for　treating　tumors,　but　its　cytotoxic　effects　and　development　of　resistance　remained　major　concerns　to　be　dealt　with.　The　aim　of　this　study　was　to　explore　the　anticancer　potential　of　survivin　regulated　CRAd　alone　or　in　combination　with　cisplatin　in　the　A549　lung　cancer　cell　line　and　cisplatin-resistant　lung　cancer　cell　line,　A549-DDPR.　Methods.　CRAd　was　genetically　engineered　in　our　laboratory　by　removing　its　E1B　region　and　adding　survivin　promoter　to　control　its　replication.　A549,　H292,　and　H661　lung　cancer　cell　lines　were　procured　from　the　CAS-China.　The　anti-tumor　effectiveness　of　combined　treatment　(cisplatin　plus　CRAd)　was　evaluated　in　vitro　through　MTS　assays　and　in　vivo　through　mouse　model　experimentation.　RT-PCR　was　used　to　assess　MDR　gene　and　mRNA　expression　of　coxsackie　adenoviral　receptor　(CAR).　Results.　Results　of　in　vitro　studies　established　that　A549　lung　cancer　cells　were　highly　sensitive　to　cisplatin　showing　dose-dependent　inhibition.　The　resistant　cells　of　A549-DDPR　exhibited　very　less　sensitivity　to　cisplatin　but　were　infected　with　CRAd　more　efficiently　as　compared　to　A549.　A549-DDPR　cells　exhibited　higher　expression　of　MDR　gene　and　CAR　in　the　RT-PCR　analysis.　The　nearly　similar　rise　in　the　CAR　expression　was　seen　when　lung　cancer　cell　lines　received　cisplatin　in　combined　treatment　(cisplatin　plus　CRAd).　Combined　anti-cancer　therapy　(cisplatin　plus　oncolytic　virus)　proved　more　efficient　than　monotherapy　in　the　killing　of　cancer　cells.　Results　of　in　vivo　experiments　recapitulated　nearly　similar　tumor　inhibition　activities.　Conclusion.　This　study　highlighted　the　significant　role　of　survivin　in　gene　therapy　as　it　has　the　potential　to　render　CRAd　more　tumor　specific.　It　also　establishes　that　higher　CAR　expression　plays　a　vital　role　in　the　success　of　adenovirus-based　therapies.　Furthermore,　a　careful　combination　of　chemotherapy　drugs　and　oncolytic　viruses　can　culminate　in　significant　therapeutic　achievements　against　cancer.